Cells identified that enhance tumor growth and suppress anti-cancer immune attack

A study led by St. Jude Children’s Research Hospital scientists has identified the population of white blood cells that tumors use to enhance growth and suppress the disease-fighting immune system. The results, which appear in the December 18 edition of the scientific journal Immunity, mark a turning point in cancer immunology and provide the foundation for developing more effective immunotherapies.
For years, researchers have known that a diverse group of white blood cells called myeloid-derived suppressor cells (MDSC) are more abundant in cancer patients than in healthy individuals. The cells enhance cancer growth and suppress the specialized T cells that target and destroy tumor cells. MDSCs have a common origin in the bone marrow, but leave to travel throughout the body and become immune cells with different functions. Blocking T cells is one of the main MDSC functions.
Until now, however, efforts to distinguish among the cell types and identify the population responsible for anti-tumor immune suppression have fallen short. The puzzle has hampered efforts to harness the immune system to fight disease.
"We have identified the monocytic cells as the important cell to target, not only in cancer but possibly for treatment of autoimmune disorders like rheumatoid arthritis or inflammatory bowel diseases where dampening the immune response could provide relief," said corresponding author Peter Murray, Ph.D., a member of the St. Jude departments of Infectious Diseases and Immunology. "We also identified growth factors and other molecules essential to the survival and function of these monocytic cells. Targeting these molecules could lead to more precise approaches for controlling the immune response at the tumor site.
"This study marks a significant step in efforts to understand, develop and optimize immunotherapies for treatment of cancer," he said

Blincyto:for the treatment of Philadelphia chromosome-negative relapsed /refractory B cell precursor acute lymphoblastic leukemia

Blincyto (blinatumomab)Approved Dec. 2014: is an immunotherapy. It engages the body’s T-cells, a type of white blood cell or lymphocyte, to destroy leukemia cells. The drug acts as a connector between a protein called CD19, which is found on the surface of most B-cell lymphoblasts, and CD3, a protein on T-cell lymphocytes.
Blincyto is specifically indicated for the treatment of Philadelphia chromosome-negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia.
Blincyto is supplied as a solution for intravenous infusion. Hospitalization is recommended for the first 9 days of the first cycle and the first 2 days of the second cycle. For all subsequent cycle starts and reinitiation (eg, if treatment is interrupted for 4 or more hours), supervision by a healthcare professional or hospitalization is recommended. Do not flush the Blincyto infusion line, especially when changing infusion bags. Flushing when changing bags or at completion of infusion can result in excess dosage and complications. The recommended dosing schedule is as follows:
A single cycle of treatment of Blincyto consists of 4 weeks of continuous intravenous infusion followed by a 2-week treatment-free interval.
• For patients at least 45 kg in weight:
- In Cycle 1, administer Blincyto at 9 mcg/day on Days 1–7 and at 28 mcg/day on Days 8–28.
- For subsequent cycles, administer Blincyto at 28 mcg/day on Days 1–28.
• Allow for at least 2 weeks treatment-free between cycles of Blincyto.
• A treatment course consists of up to 2 cycles of Blincyto for induction followed by 3 additional cycles for consolidation treatment (up to a total of 5 cycles).

Adverse effects associated with the use of Blincyto may include, but are not limited to, the following:

• pyrexia
• headache
• peripheral edema
• febrile neutropenia
• nausea
• hypokalemia
• tremor
• rash
• constipation

In addition, Cytokine Release Syndrome (CRS) and neurological toxicities, both of which may be severe, life-threatening, or fatal, occurred in patients receiving Blincyto. Interrupt or discontinue Blincyto as recommended.

For additional information regarding Blincyto or Philadelphia chromosome-negative relapsed /refractory B cell precursor acute lymphoblastic leukemia, please visit www.amgen.com

New Cancer Therapy Drug: Gilead; for the treatment of relapsed CLL, follicular B-cell NHL

Zydelig (idelalisib) is a small molecule inhibitor of phosphoinositide-3 kinase (PI3K) delta, an intracellular signaling component. PI3K-delta is expressed primarily in blood-cell lineages, including cells that cause or mediate hematologic malignancies.
Zydelig is specifically indicated for the following:

• Relapsed chronic lymphocytic leukemia in combination with rituximab, in patients for whom rituximab alone would be considered appropriate therapy due to other co-morbidities.
• Relapsed follicular B-cell non-Hodgkin lymphoma in patients who have received at least two prior systemic therapies. 
• Relapsed small lymphocytic lymphoma in patients who have received at least two prior systemic therapies

Zydelig is supplied as a tablet for oral administration. The recommended maximum starting dose of Zydelig is 150 mg administered orally twice daily. Zydelig can be taken with or without food. Tablets should be swallowed whole. Continue treatment until disease progression or unacceptable toxicity.

Adverse effects associated with the use of Zydelig may include, but are not limited to, the following:
diarrhea
pyrexia
fatigue
nausea
cough
pneumonia
abdominal pain
chills
rash

For additional information regarding Zydelig or relapsed chronic lymphocytic leukemia, relapsed follicular B-cell non-Hodgkin lymphoma and relapsed small lymphocytic lymphoma, please visit www.zydelig.com

U.S. Approves Skin Cancer Treatment

U.S. regulators Monday approved Bristol-Myers Squibb Co. ’s Opdivo for advanced skin cancer, the latest drug to reach the market in the emerging field of cancer immunotherapy.
The decision by the Food and Drug Administration means Bristol-Myers now has two drugs on the market that work by unleashing the body’s immune system to attack tumors, helping to solidify the company’s lead in an area of cancer treatment that has drawn wide interest across the pharmaceutical industry.
It also comes amid a flurry of year-end drug approvals by the federal agency, including three last Friday. Opdivo, which is also known by the chemical name nivolumab, is the eighth new drug to reach the market in the past four years for late-stage melanoma, a historically lethal disease.
Bristol-Myers officials said the company plans to charge an average of $12,500 a month for the treatment, the same price as the rival drug Keytruda from Merck & Co., which was approved in September. Both drugs target a protein called PD-1, a molecular brake that prevents the immune system from seeing tumors as invaders and enables cancer to avoid attack.
The two drugs are approved for patients who fail to respond to certain other medicines including Yervoy, another Bristol-Myers immunotherapy drug that was approved for advanced melanoma in 2011 and that works by releasing a different immune system brake.
All three drugs belong to a class of agents known as checkpoint inhibitors that, by unleashing an immune system attack against cancer, are enabling significant numbers of patients to live years longer than would otherwise be expected. Roche Holding AG and AstraZeneca PLC are among other companies testing agents against immune system brakes.
Approval of Opdivo “is a confirmation of the strength of our strategy” to focus the company’s efforts on cancer immunotherapy, said Giovanni Caforio, Bristol-Myers’s chief operating officer. “The ability to come to the market with a second very important medicine is something we’ve been working for and we’re very proud of it.”
The approval, which came under the FDA’s so-called breakthrough designation initiative, was based on the experience of 120 participants in a continuing clinical trial, among whom 32% had significant tumor shrinkage. The effect lasted for more than six months in about one-third of such patients, the FDA said.
The most serious side effects included a severe immune response against healthy organs, including the lung, and were generally managed by using aggressive treatment with steroids.

Cancer drug developer caps busy year for IPOs, especially by biotech firms

Juno Therapeutics Inc. shares surged 63% in their market debut Friday, after a flurry of demand for the year’s last expected new offering led the biotech firm to price above its already-boosted range.
Juno, which develops cancer treatments that use the body’s own immune system to fight the disease, began trading Friday on the Nasdaq at $39 a share JUNO, +45.83% after pricing 11 million shares at $24.
The open price of $39 values Juno at more than $3 billion, the largest valuation for a biotech going public since IPO research firm Renaissance Capital began tracking this kind of data a little over a decade ago. Juno’s valuation comes despite the fact that the biotech has no revenue, has never reported a profit and has no drug candidates in late-stage trials.

I.P.O. of Juno Therapeutics, Developer of a Cancer Treatment, Excites Investors

Excitement over a promise of a new type of cancer treatment ignited a frenzy on Wall Street Friday as a little-known year-old company pulled off one of the largest initial public stock offerings in the biotechnology sector.

The company, Juno Therapeutics, sold 11 million shares at $24 each on Thursday in its initial public offering. The company increased its price and the number of shares offered earlier that day after a surge in demand.

When trading started on Friday, the stock soared, closing at $35 a share, up 46 percent, and giving Juno a market valuation of about $2.7 billion.

Juno, based in Seattle, is working on sophisticated treatments that genetically engineer the body’s immune cells so they can better recognize and kill cancer cells. Its approach has been tried so far on a relatively small number of patients, but the results have been extraordinary. Some people with leukemia have been rescued from near-certain death. A study of one of Juno’s drugs found an 89 percent remission rate among 27 adults with acute lymphoblastic leukemia no longer responding to other treatments.

Juno has collaborations with the Fred Hutchinson Cancer Research Center in Seattle, Seattle Children’s Research Institute and the Memorial Sloan Kettering Cancer Center in New York, and they could be in for a windfall if the company succeeds.

In addition to the usual royalties and milestone payments that companies pay to suppliers of technology, Juno will make “success payments” to the Hutchinson center and Sloan Kettering if the company’s stock is above certain prices at certain points in time. The total payments could be as much as $375 million in cash and stock for the Hutchinson center and $150 million for Sloan Kettering.

Even before raising $264 million its public offering, Juno had raised more than $300 million privately, a large amount for such a young firm. One early investor was Jeff Bezos, head of Seattle-based Amazon. Juno’s largest shareholder, with about a 30 percent stake, is a fund that invests the State of Alaska’s oil revenue

A new strategy for developing drugs to fight Cancer and other diseases

Promising treatments known as biologics are on the market and under development for many serious illnesses such as cancer, but some of them come with high risks, even lethal ones. Now scientists have produced a novel class of molecules that could be as effective but without the dangerous side effects. They report their work on these compounds, which they tested on prostate cancer cells, in ACS' Journal of the American Chemical Society
David A. Spiegel and colleagues explain that biologics are protein-based therapies that have revolutionized cancer treatment over the past decade. These compounds work by latching onto malignant cells and then triggering the immune system to destroy them -- an approach known as immunotherapy. More than 400 kinds are currently undergoing testing in clinical trials. Although they're very effective at clearing out cancer cells, biologics have serious drawbacks -- including potentially fatal allergic reactions -- that are mainly due to their relatively large size. Spiegel's team wanted to develop an alternative that would be just as effective but without the risks.
The researchers produced a set of molecules that they call synthetic antibody mimics, or SyAMs. These molecules act like biologics by sparking an immune response but are far smaller. In lab tests, a subgroup called SyAM-Ps worked well against prostate cancer cells. Because of their small size, the researchers suggest that SyAMs could avoid many of the pitfalls that have plagued biologics. The compounds could represent an entirely new direction in immunotherapy for treating cancer and other diseases, the researchers conclude.

There are three kinds of Bone Marrow or Stem Cell Transplants

• A bone marrow transplant is a procedure to replace damaged or destroyed bone marrow with healthy bone marrow stem cells.
  Bone marrow is the soft, fatty tissue inside your bones. Stem cells are immature cells in the bone marrow that give rise to all of your blood cells.
   
• Autologous bone marrow transplant: The term auto means self. Stem cells are removed from you before you receive high-dose chemotherapy or radiation treatment. The stem cells are stored in a freezer (cryopreservation). After high-dose chemotherapy or radiation treatments, your stems cells are put back in your body to make (regenerate) normal blood cells. This is called a rescue transplant.
• Allogeneic bone marrow transplant: The term allo means other. Stem cells are removed from another person, called a donor. Most times, the donor's genes must at least partly match your genes. Special blood tests are done to see if a donor is a good match for you. A brother or sister is most likely to be a good match. Sometimes parents, children, and other relatives are good matches. Donors who are not related to you may be found through national bone marrow registries.
• Umbilical cord blood transplant: This is a type of allogeneic transplant. Stem cells are removed from a newborn baby's umbilical cord right after birth. The stem cells are frozen and stored until they are needed for a transplant. Umbilical cord blood cells are very immature so there is less of a need for matching. But blood counts take much longer to recover.

Pioneering a new Treatment that Heats the Blood, Kills Cancer Cells

A new cancer-fighting strategy that kills deadly cells by raising body temperatures is heating up in the Bay Area.
Whole body hyperthermia is a cancer therapy in which the patient’s body temperature is raised high enough to kill cancer throughout the body.
“Cancer cells are not normal.  They don’t repair themselves well, and are subject to being destroyed by methods your cells can handle,” Dr. James Lilja stated.  Doctors at San Jose’s Good Samaritan Hospital are using pioneering the research.  The method uses tubes outside the patient’s body to heat blood with hot water to well over 100 degrees before it’s re-infused.
The therapy lasts about two hours, long enough to kill only the cancer, and a special filtering system keeps the blood from going bad.
“By using this kind of a system we’re able to remove, we think some of the unknown dangerous chemicals that are released by the body,” Dr. Roger Vertrees said.
Two patients have been treated in the first clinical trial, and have been able to return to work.
“The hope for this therapy is that it becomes a standard modality for treating cancer like chemotherapy, radiation and surgery,” Dr. Vertrees said.
Good Samaritan is looking for other patients with ovarian cancer to participate in its clinical trials

Shorter Radiation therapy Not a Bad Idea

“I started my residency in 1993,” Dr. Freedman said. “That was drilled into us”: Shorter and more intense radiation therapy “was a bad idea and would have a bad cosmetic result.”

But with improved equipment and methodology, he said, the clinical trials found that cosmetic results were just as good with the shorter treatment. “They did not just publish that the cure rates were the same, but they published very in-depth cosmetic assessments, particularly the British, who took pictures that were graded by blinded observers,” he said.

“That’s when the tide started turning.”

Shorter Radiation Therapy vs the standard in Breast Cancer Treatments

In Canada and Britain, the statistics were far different. At least two-thirds of women in both groups received the shorter therapy.

In the United States, total medical expenses for the shorter therapy in women for whom it was endorsed were $28,747. For comparable women receiving the longer course of treatment, the cost was $31,641. For the second group of women — for whom the shorter therapy was neither endorsed nor discouraged — medical costs were $64,723, compared with $72,860 for conventional therapy. Health insurers pay for radiation in a piecemeal fashion, and the shorter course involves about 16 doses, compared with about 33 with the conventional therapy.

Dr. Harold J. Burstein, a medical oncologist at Dana-Farber Cancer Institute in Boston, said that when the initial results of a Canadian trial on the shorter therapy were published in 2002, “there was real ambivalence about changing practice based on one study.” Doctors wanted to see what would happen as the women were followed over a longer time, and they wanted to see the result confirmed.

The results of that study contradicted years of practice in the field, said Dr. Gary M. Freedman, a breast radiation oncologist at the University of Pennsylvania and an author of the new study. In the 1970s and 1980s, when equipment was much less sophisticated, radiation oncologists found that shorter and more intense therapy burned women’s skin and scarred their breasts, making them shrivel and shrink over the ensuing decade.

A New study on Radiation in Breast Cancer Therapies

In the new study, published Wednesday in JAMA, The Journal of the American Medical Association, two University of Pennsylvania doctors, Ezekiel J. Emanuel and Justin E. Bekelman, and their colleagues analyzed data from 14 commercial insurance plans involving 15,643 women who had their breasts irradiated after lumpectomies.

Radiation is used after women have lumpectomies because it reduces the odds that another cancer will arise in the breast, and it improves the chances of survival.

The researchers considered two groups of women who had radiation therapy and asked how many had received the shorter course. One group closely matched women in the previous randomized studies that evaluated the conventional treatment versus the shorter one. These women were older than 50 and had early-stage cancers. Practice guidelines published in 2011 by the American Society for Radiation Oncology recommend the shorter radiation therapy for this group.

The other group differed from participants in the previous studies because they were younger, had had prior chemotherapy or had cancer cells in their lymph nodes, indicating a more advanced cancer. The practice guidelines neither endorse nor discourage the shorter therapy for these women.

Use of the shorter course of radiation increased in both groups of women from 2008 to 2013, but still only a minority received this treatment. In the group that should have received the shorter therapy under the guidelines, 10.6 percent received it in 2008 and 34.5 percent in 2013. In the group that received no recommendation for or against the shorter treatment, the percentage who used it rose from 8.1 percent to 21.2 percent over that time.

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In Canada and Britain, the statistics were far different. At least two-thirds of women in both groups received the shorter therapy.

Long radiation treatments faulted in many Breast Cancer cases

Two-thirds of women who have lumpectomies for breast cancer are receiving radiation treatment that lasts nearly twice as long as necessary, a new study reports.

The conventional, longer treatment lasts five to seven weeks. But four rigorous studies and guidelines from a leading radiology society conclude that three to four weeks of more intense radiation is just as effective.

Women overwhelmingly prefer the shorter course of radiation, studies have found. It is also less expensive.

Even though 60 to 75 percent of women with breast cancer have lumpectomies — a total of about 140,000 to 160,000 women — doctors and health insurers say relatively few are receiving the shorter treatment because it takes time to change ingrained medical practices, especially when a procedure has been used for decades and the new one offers no additional medical benefit. Its advantages are saving time for patients, and money for the health care system and insurers.

“If a physician is doing five to seven weeks of radiation for 25 years, particularly if the physician is not a specialist and not in an academic medical center, you will be a bit leery about going to something new,” said Dr. Bruce G. Haffty, a professor and chairman of the department of radiation oncology at the Rutgers Cancer Institute of New Jersey. “You are comfortable with the outcomes, patients are satisfied. Now you’ve got something that perhaps costs a bit less, but you wonder: Is it as effective?”

New Cancer Treatments Represent Major Breakthroughs

Corey Wood was a week away from her graduation from the University of California at Berkeley when she started getting flashes in one of her eyes. Her doctor was concerned and had an inkling that something serious was going on, so he took the unusual step of ordering a body scan. Corey was a healthy 22 year old who was tremendously fit and who had already completed eight marathons. Yet, stunningly, her tests revealed that she had stage IV lung cancer. The flashing of light she was experiencing was caused by a tumor behind her eye. But the disease was also in her lungs where there were multiple tumors and the disease had rapidly metastasized to her bones. Her prognosis wasn’t very good.
However, a sample of her tumor was sent to Foundation Medicine for genomic analysis and it was found that her cancer was being driven by an ROS-1 genetic alteration. Fortunately, a drug had been recently approved to treat this very type of cancer – Pfizer’s Xalkori (crizotinib). Xalkori is one of the new generation of drugs called targeted therapies, drugs specifically designed to treat Corey’s ROS-1 driven cancer in a way that does not cause the concomitant horrific side effects associated with traditional chemotherapy. After taking two Xalkori pills a day for three months, all the while going about her normal activities, Corey was cancer free.
Corey shared her inspirational story yesterday at the Forbes Healthcare Summit held in New York City. The eradication of her disease shows the power of the tools available to treat cancer that were thought of as science fiction just a decade ago, such as whole body scanning, genomic analysis of her tumor, and having a targeted drug available in the pharmacy to eradicate her disease. This approach to treating cancer is only going to get better. There are hundreds of targeted therapies in development in the pipelines of dozens of biopharmaceutical companies. There are other breakthroughs being made as well, particularly in the exploding field of immuno-oncology where drugs such as Yervoy (Bristol-Myers Squibb) and Keytruda (Merck) are helping to stimulate a cancer patient’s immune system to fight the cancer. These are incredibly exciting times.
After Corey’s talk, Forbes’ Matt Herper led a panel discussion with Peter Bach (Memorial Sloan Kettering Cancer Center), Bob Hugin (CEO, Celgene CELG +0.41%), Richard Klausner (CMO, Illumina ILMN -1.42%), and Sandra Swain (Medical Director, Washington Cancer Institute). The session tried to answer the question “Are we at a tipping point for cancer and are we on the doorstep of vanquishing this disease?” This was a great discussion about changing treatment paradigms, access to healthcare, and emerging science. But Bach brought the group to the key issue facing oncology – the costs of treatment. Yervoy and Keytruda are great drugs, but they cost $120,000 and $150,000 per year, respectively. Furthermore, these drugs are not going to be used as stand-alone agents. Rather they will be used in combination with other drugs such as targeted therapies.
The good news is in the not too distant future, a cancer diagnosis will not be a death sentence. Rather, this will be a treatable condition controlled by taking a combination of these breakthrough therapies. However, people may require a combination of these therapies for the rest of their lives. Imagine millions of people needing a cocktail of three drugs, each of which costs $100,000/year/patient. It doesn’t take major economic analyses to realize that the costs inflicted on the healthcare system will not be sustainable in such a scenario

On Targeted Therapies for Cancer

It has only been recently that the understanding of the atlas, the periodic table of changes that are resident within cancer cells, the spectrum of mutations that occur in various cancers, be it breast,  prostate or colon. Without knowledge of that periodic table, without knowledge of the genes that are aberrant in those cancers, it’s very difficult to treat those cancers with therapies that are squarely against impacting that specific cancer. If we could have an understanding of those genetic mutations then we would be able to develop targeted therapies for those cancers, and have those cancers elicit more durable responses for patients with the disease. The approach that has been taken for decades, is one of a more general approach to cancer, that involves chemotherapy, radiation and surgery, which have made a huge impact on the cancer problem, but we’re now at the threshold of a time where we can begin to understand exactly what’s wrong in a person’s cancer and tailor the therapies.

A possible Vaccine for Cancer ?

The vaccine that is being referred to is for a particular type of breast cancer called HER2-positive breast cancer. So there‘s a receptor that drives that disease and the drug Herceptin is used for those patients so that drug plus surgery and radiation has led to significant improvement in survival, but there are still some patients that recur and ultimately succumb to the disease. Elizabeth Mittendorf, who led a trial at MD Anderson Cancer Center, asked the question: "After treatment if we were to give those patients several rounds of this vaccine, which has this abnormal HER2 protein packaged in it, would we reduce the rate of recurrence?’ The results were striking. We had a very significant reduction in the recurrence of rates with about a 50 percent reduction which will translate into thousands of lives each year with women with that particular breast cancer."

Manipulating Immune Cells to Fight Cancer is Working!

“It’s not just a handful of patients. It’s an expanding number at multiple centers,” says Renier Brentjens, MD, PhD, an oncologist at Memorial Sloan Kettering Cancer Center, who has spent 20 years researching ways to manipulate immune cells to fight cancer. “That’s often an indication that you’re not looking at a one-patient thing or a fluke. It really works in this disease.”

Since 2009, researchers at Sloan Kettering, the University of Pennsylvania, and the National Cancer Institute have tried this treatment on about 100 patients with ALL. More than 70 have gone into complete remission. Results like this earned the treatment its breakthrough status at the FDA.

“This is a very, very bad disease. The 3-year overall survival after relapse is less than 10%,” Brentjens says. “Most of the patients that we’ve seen for a 6-month visit after the T-cell therapy are at or past what their expected survival was when they first came into our clinic.”

Researchers continue testing modified T-cells in patients with other types of leukemia, lymphoma, and myeloma -- all blood cancers. “The question is: Can we expand this technology to more common tumors? Colon cancer, ovarian cancer, breast cancer,” Brentjens says. Early research in this area says the answer could be “yes."

Immunotherapy Brings New Hope to Cancer Fight

The treatment, called CAR T-cell therapy, re-engineers a patient’s own immune system to recognize and attack cancer cells. This July, FDA gave CAR T-cell therapy "breakthrough therapy" designation, which fast-tracks its path to FDA approval.

CAR T-cell therapy is a type of immunotherapy, a new wave of experimental and newly approved treatments that spur the immune system to fight cancer like it does other illnesses. Immunotherapy dominated talks at this year’s American Society of Clinical Oncology meeting. Some doctors and scientists are calling it the pathway to a cure. This year the FDA has approved two more immunotherapy drugs for the treatment of melanoma and chronic lymphocytic leukemia, including pembrolizumab (marketed as Keytruda), which was approved for melanoma last month.

“We are supercharging the immune system” says Lynn Schuchter, MD, chief of hematology oncology and an immunotherapy researcher at the University of Pennsylvania. “This brings a totally new dimension to attacking a cancer cell.”

New Vaccine for Breast Cancer

The study, published in Clinical Cancer Research, also suggests the vaccine primes patients' white blood cells to attack tumor cells, slowing down the progression of the cancer.
The new vaccine works by targeting a protein called mammaglobin-A that is predominantly found in breast tissue. Its role in healthy tissue is currently unknown, but previous research has shown that breast tumor cells express the protein at abnormally high levels.
"Being able to target mammaglobin is exciting because it is expressed broadly in up to 80% of breast cancers, but not at meaningful levels in other tissues," says senior author Dr. William Gillanders. "In theory, this means we could treat a large number of breast cancer patients with potentially fewer side effects."
Many pre-existing drug treatments for breast cancer target another protein called human growth factor receptor 2 (HER2). These treatments, including trastuzumab and pertuzumab, can have side effects that include diarrhea and heart problems.

Bone Marrow, or Stem Cell Transplant alternate names

Transplant - bone marrow; Stem cell transplant; Hematopoietic stem cell transplant; Reduced intensity, nonmyeloablative transplant; Mini transplant; Allogenic bone marrow transplant; Autologous bone marrow transplant; Umbilical cord blood transplant

Outlook (Prognosis) of Stem Cell Transplant

How well you do after transplant depends on:

• The type of bone marrow transplant
• How well the donor's cells match yours
• What type of cancer or illness you have
• Your age and overall health
• The type and dosage of chemotherapy or radiation therapy you had before your transplant
• Any complications you may have

A bone marrow transplant may completely or partially cure your illness. If the transplant is a success, you can go back to most of your normal activities as soon as you feel well enough. Usually it takes up to 1 year to recover fully.
Complications or failure of the bone marrow transplant can lead to death.

After the Bone Marrow or Stem Cell Transplant

A bone marrow transplant is usually done in a hospital or medical center that specializes in such treatment. Most of the time, you stay in a special bone marrow transplant unit in the center. This is to limit your chance of getting an infection.
Depending on the treatment and where it is done, all or part of an autologous or allogeneic transplant may be done as an outpatient. This means you do not have to stay in the hospital overnight.
How long you stay in the hospital depends on how much chemotherapy or radiation you received, the type of transplant, and your medical center's procedures. While you are in the hospital, you will be isolated because of the increased risk of infection. The health care team will closely monitor your blood count and vital signs.
While you are in the hospital you may:

• Receive medications to prevent or treat infections, including antibiotics, antifungals, and antiviral drugs
• Need many blood transfusions
• Be fed through a vein (IV) until you can eat by mouth and stomach side effects and mouth sores have gone away
• Be given medications to prevent graft-versus-host disease

Before the Stem Cell or Bone Marrow Transplant

Your health care provider will ask about your medical history and do a physical exam. You will have many tests before treatment begins.
Before transplant, you will have one or two tubes, called catheters, inserted into a blood vessel in your neck or arms. This tube allows you to receive treatments, fluids, and sometimes nutrition.
Your doctor or nurse will likely discuss the emotional stress of having a bone marrow transplant. You may want to meet with a mental health counselor. It is important to talk to your family and children to help them understand what to expect.
You will need to make plans to help you prepare for the procedure and handle tasks after your transplant:

• Complete an advance care directive
• Arrange medical leave from work
• Take care of bank or financial statements
• Arrange care of pets
• Arrange for someone to help with household chores
• Confirm health insurance coverage
• Pay bills
• Arrange for care of your children
• Find housing for yourself or your family near the hospital, if needed

Complications of a Bone Marrow Transplant can included

• Anemia
• Bleeding in the lungs, intestines, brain, and other areas of the body
• Cataracts
• Clotting in the small veins of the liver
• Damage to the kidneys, liver, lungs, and heart
• Delayed growth in children who receive a bone marrow transplant
• Early menopause
• Graft failure, which means that the new cells do not settle into the body and start producing stem cells
• Graft-versus-host disease, a condition in which the donor cells attack your own body
• Infections, which can be very serious
• Inflammation and soreness in the mouth, throat, esophagus, and stomach, called mucositis
• Pain
• Stomach problems, including diarrhea, nausea, and vomiting

Complications of a Bone Marrow Transplant depend on many things

• The disease you are being treated for
• Whether you had chemotherapy or radiation before the bone marrow transplant and the dosages of such treatments 
• Your age
• Your overall health
• How good of a match your donor was
• The type of bone marrow transplant you received (autologous, allogeneic, or umbilical cord blood)

Risks of a Bone Marrow Transplant

A bone marrow transplant may cause the following symptoms:

• Chest pain
• Chills
• Drop in blood pressure
• Fever
• Flushing
• Funny taste in the mouth
• Headache
• Hives
• Nausea
• Pain
• Shortness of breath

Why the Procedure is Performed

A bone marrow transplant replaces bone marrow that either is not working properly or has been destroyed (ablated) by chemotherapy or radiation. Doctors believe that for many cancers, the donor's white blood cells can attach to any remaining cancer cells, similar to when white cells attach to bacteria or viruses when fighting an infection.
Your doctor may recommend a bone marrow transplant if you have:

• Certain cancers, such as leukemia, lymphoma, and multiple myeloma
• A disease that affects the production of bone marrow cells, such as aplastic anemia, congenital neutropenia, severe immunodeficiency syndromes, sickle cell anemia, thalassemia  
• Had chemotherapy that destroyed your bone marrow

Donor stem cells can be collected in two ways

• Bone marrow harvest. This minor surgery is done under general anesthesia. This means the donor will be asleep and pain-free during the procedure. The bone marrow is removed from the back of both hip bones. The amount of marrow removed depends on the weight of the person who is receiving it.
• Leukapheresis. First, the donor is given 5 days of shots to help stem cells move from the bone marrow into the blood. During leukapheresis, blood is removed from the donor through an IV line in a vein. The part of white blood cells that contains stem cells is then separated in a machine and removed to be later given to the recipient. The red blood cells are returned to the donor.

Before the transplant, chemotherapy, radiation, or both may be given

• Ablative (myeloablative) treatment: High-dose chemotherapy, radiation, or both are given to kill any cancer cells. This also kills all healthy bone marrow that remains, and allows new stem cells to grow in the bone marrow.
• Reduced intensity treatment, also called a mini transplant: Patients receive lower doses of chemotherapy and radiation before a transplant. This allows older patients, and those with other health problems to have a transplant.

A stem cell transplant is usually done after chemotherapy and radiation is complete. The stem cells are delivered into your bloodstream usually through a tube called a central venous catheter. The process is similar to getting a blood transfusion. The stem cells travel through the blood into the bone marrow. Most times, no surgery is needed.

Bone marrow transplants cancer treatment

A bone marrow transplant is a procedure to replace damaged or destroyed bone marrow with healthy bone marrow stem cells.
Bone marrow is the soft, fatty tissue inside your bones. Stem cells are immature cells in the bone marrow that give rise to all of your blood cells.
There are three kinds of bone marrow transplants:

• Autologous bone marrow transplant: The term auto means self. Stem cells are removed from you before you receive high-dose chemotherapy or radiation treatment. The stem cells are stored in a freezer (cryopreservation). After high-dose chemotherapy or radiation treatments, your stems cells are put back in your body to make (regenerate) normal blood cells. This is called a rescue transplant.
• Allogeneic bone marrow transplant: The term allo means other. Stem cells are removed from another person, called a donor. Most times, the donor's genes must at least partly match your genes. Special blood tests are done to see if a donor is a good match for you. A brother or sister is most likely to be a good match. Sometimes parents, children, and other relatives are good matches. Donors who are not related to you may be found through national bone marrow registries.
• Umbilical cord blood transplant: This is a type of allogeneic transplant. Stem cells are removed from a newborn baby's umbilical cord right after birth. The stem cells are frozen and stored until they are needed for a transplant. Umbilical cord blood cells are very immature so there is less of a need for matching. But blood counts take much longer to recover.

New tool to guide Cancer Care in patients

Researchers must show that the drug predictions that seem so promising in a dish actually work in patients. They also will need to deal with technological issues, such as the time it takes to grow patients’ tumor cells in a dish, between two and six months in the study, and not every attempt was successful.

“For decades, literally decades, people have wanted to do patient-specific chemotherapy sensitivity testing, and it’s been a very hard problem,” said Dr. James Eshleman, a professor of pathology and oncology at Johns Hopkins University School of Medicine, who was not involved in the work. “One problem which is totally counterintuitive is that cancers grow in patients just fine, but” in a dish, “it’s relatively hard to generate cell lines, and specific cancers are extraordinarily difficult, largely for reasons that we don’t understand.”

The researchers believe that with time, those technological issues can be resolved. The study used an imperfect source of cells, leftovers taken from biopsies that had been done for other purposes. If the biopsies were taken with the idea of growing cells and testing drugs, it is likely that the process could be quicker and more efficient.

A far bigger question looms: Sometimes, therapies that seem like a home run in laboratory tests or even animal models of cancer do not work in people.

“This is really setting up the criteria for what we have to look at next,” Schlegel said. “Someone has to figure out if we grow up these cells, how many times is this going to be an adequate predictor of patient response?”

Engelman said he already is beginning to work on the answer to that question.

His team will start by reexamining clinical trials in which patients received drugs and their responses were known. Researchers will then grow cells harvested from their tumors in a dish to see whether the people who had the best responses to the drug also happened to have cells that were more sensitive to the treatment, as researchers would expect.

If that work shows promise, it will help provide the evidence needed to begin using the tool to guide cancer care in patients.

Study points to new Direction for Cancer Therapies

In the new study, the researchers started with 55 samples of cancer cells that had developed resistance to a targeted drug. Nearly half of the cells had been harvested directly from lung cancer patients whose cancer had returned.

The researchers then used a relatively new technique to grow those cancer cells in a dish, establishing a population of cells that could be used to screen for possible treatments.

Next, the scientists bombarded those cancer cells with an array of 76 different drugs and watched to see which ones would be effective. In 45 cases, they found that a novel drug combination worked; the cancer cells became resensitized to the initial drug that had stopped working.

Outside researchers said the study pointed to a future direction for care and was exciting because some of the drug combinations could not have been predicted by genetic testing alone. Dr. Richard Schlegel, director of the Center for Cell Reprogramming at Georgetown University School of Medicine, said the work was “a mirror into the future” of cancer care.

But significant hurdles still exist before the tool could be used to direct a drug regimen.

Doctors look to personalize Cancer Care

A group of Boston physicians and researchers has taken a crucial step toward personalized cancer treatment, identifying novel drug combinations that show promise against cancer cells that have developed a resistance to therapy.

The technology is not yet ready for the ultimate test, in which the promising drug combinations are given directly to patients. However, the researchers saw tantalizing hints of the potential of the approach when they grew a handful of the drug-resistant cancers in mice and observed that in all cases, the new drug regimens were effective at shrinking tumors.

“You could imagine in the future, maybe the not-too-distant future, we could start to do this as clinical trials where we would assign patients to treatments based on the results of what their cancer cells showed susceptibility to,” said Dr. Jeffrey Engelman, director of thoracic oncology at Massachusetts General Hospital, who co-led the work published Thursday in the journal Science. A revolution in medicine has made genetic testing of tumors almost routine when selecting treatment for many types of cancer. However, resistance to targeted therapy almost invariably develops and genetic clues, though powerful, have not always been sufficient to identify the best treatment.

That has spurred a range of efforts to personalize treatment and monitor cancer’s evolution. This summer, a Mass. General team showed that it was possible to isolate rare tumor cells circulating in the blood and analyze them to understand how a patient’s cancer was changing. Other researchers have been working on developing mouse avatars, in which a patient’s tumor is grown in a lab animal in which new therapies can be tested.

A new method using a Patient’s drug-resistant tumor cells to screen for effective Therapies

In collaboration with Cyril Benes, also at Massachusetts General, Engelman’s team developed a method using a patient’s drug-resistant tumor cells to screen for effective therapies. Starting with a tiny amount of tumor tissue from a biopsy, the scientists grew patient cells in a dish until they had enough to perform drug screening. They then tested those cells against 76 cancer drugs.
By combining the drug screening and traditional genetic analyses, the team successfully identified treatment combinations that killed cells in 45 of 55 drug-resistant tumor cell lines tested.
The team didn’t use the resulting drug combinations to alter or guide any patient’s treatment regimens, Engelman said. Before that can be done, the method needs to be evaluated in a randomized clinical trial to see whether the drug combinations that kill cancer cells in a dish are similarly effective in patients, he said.
In addition, the team spent months coaxing the patient cells to grow into large enough populations for the drug screening. To be useful to a cancer patient undergoing treatment, that process needs to take weeks, not months.
“What we’ve done is quite modest,” Engelman said. “What’s exciting now is whether we can take it to that next step -- use it to inform how we treat patients.”

New Cancer Technique Outsmarts Cells Resisting Treatment

By directly screening patient cancer cells, researchers have created a new way to identify potential treatments to effectively attack drug-resistant tumors.
While the screening system has only been used on tumor cells in a dish and in mice, the method could someday lead to individualized drug treatment strategies that adapt even as a patient’s tumor changes.
“The results have been promising enough where we are looking to see if we can develop this now to direct patient treatments,” said Jeffrey Engelman, a medical oncologist at Massachusetts General Hospital in Boston and co-senior author of the study released online today by the journal Science.
Targeted therapies are drugs that interfere with specific cancer-promoting pathways in tumor cells. They have been more effective than traditional chemotherapy drugs against tumors, though the effect usually lasts only one to two years. Tumors rapidly mutate to use alternate pathways, like back alleys, to bypass the original pathways blocked by the medicines.
To combat that resistance, researchers typically analyze DNA from a biopsy of a drug-resistant tumor to try and identify the resistance-causing mutation, then pick a new drug to block that alternate pathway as well. This approach has met with limited success because most genetic results are ambiguous or don’t directly point to treatment strategies, Engelman said.

Is it better to get Cancer Therapy at night?

“The study developed out of a mistake. We accidentally omitted a synthetic steroid…from the medium in which we routinely grow mammary gland cells,” “And we noticed that the cells acquired a faster rate of migration when we followed them under a microscope.”
Intrigued, they turned to mice to answer some more questions. Knowing that steroid levels peak during the day and drop off during sleep, Yarden and his colleagues wondered whether the timing of anti-tumor drugs would affect tumor growth. So they gave a group of mice with breast cancer tumors lapatinib at different times over a 24-hour period and tracked any differences in the size and growth of the tumors.
Indeed, the mice given the drug while they slept showed significantly smaller tumors after seven days than those who received the drug during the day. Yarden suspects that the lower levels of steroid hormones circulating at night allows more of the EGF-targeting drug to hone in on its receptors on the tumor cells and inhibit their growth. Not only that, but the tumors in the mice taking the drug at night looked different; they showed less blood vessel infiltration which meant they were less robust.
Does that mean it’s better to get cancer therapy at night? So far, the results only apply to animal models, and to cancers driven by EGF. More work needs to be done, but if it’s validated, shifting therapies to just before bed “seems logical,” says Yarden. Especially since drugs like lapatinib come in pill form, so it would be relatively easy to take medications before turning in rather than in the morning.

The body doesn't process drugs in the same way throughout the day

It’s news to no one that your body works differently when you’re awake and when you’re sleeping. But could the different states also affect how your body processes certain life-saving drugs? Researchers, reporting Friday in the journal Nature Communications, found that when it comes to cancer drugs, the answer may be yes.
Researchers at the Weizmann Institute of Science discovered—by happy accident—that some of the body’s molecular functions during the day may interfere with the effectiveness of certain cancer medication. Specifically, they found that the normal day-time production of some steroid hormones in the body actually inhibited the work of epidermal growth factor (EGF) receptors—which are the proteins targeted by a class of anti-cancer drugs. Tumor cells plant these receptors on their surfaces to attract nutrients that help them survive and grow. Drugs, including the breast cancer agent lapatinib, can block these receptors on tumors, and such medications are a popular way to treat breast cancers expressing epidermal growth factor.
But Yosef Yarden, a professor in the department of biological regulation, and his team found that when the tumor cells simultaneously bind to something else—such as steroid hormones—the EGF receptors are less active, making drugs like lapatinib less potent.
The findings are still preliminary, but there is other evidence that the day-night cycle may be a potentially important factor in determining cancer treatment dosing in coming years. Some studies showed, for example, that when the 24-hour rest and activity cycle is broken metabolically, and the EGF receptors aren’t given enough time to be active, certain tumors in animals grow two to three times faster.

Why Cancer Drugs May Work Better While You Sleep

The combination, he says, may be more effective since one drug works to suss out tumor cells, like shining a molecular spotlight on them, while the other builds up the body’s defenses against them, allowing immune cells to better target and eliminate cancers.
The time that both groups of patients enjoyed before their melanoma recurred, however, was similar. But Hodi and his team note that the inflammation caused as a side effect of the drugs could be interpreted as early tumor sites, leading researchers to record the presence of tumors that may not be there.
Teasing apart that issue and determining the safe and optimal doses of the combination will require more studies, says Hodi. The dose of ipilimumab he used, for example, was higher than the one approved by the FDA in 2011, since this study was begun before the agency approved the drug. But the idea that a combination of powerful immune-based drugs could help cancer patients fight their disease and survive longer is encouraging. “This world of [new cancer treatments] is moving fast, and there are a slew of possible combinations that others are studying now,” he says. “It’s where the future of cancer therapy will be.”

Promising New Cancer Treatment Uses Immune Cells

Cancer researchers are pumping out study after study trying to figure out how best to use the body’s own immune system to fight cancer tumors.
Scientists led by Dr. F. Stephen Hodi at Dana Farber Cancer Institute show for the first time that combining two drugs that target the immune system in different ways could help melanoma patients survive longer. From 2010 to 2011, 245 patients with advanced skin cancer who had not responded to at least one previous treatment were randomly assigned to get a newly approved drug, ipilimumab, designed to help the immune system better target tumors, either alone or in combination with another drug. Ipilimumab (marketed as Yervoy), was among the first anti-cancer medications that allows immune cells to “see” tumors better; since tumors grow from originally normal cells, the immune system often gives them a pass and doesn’t attack them as foreign. But drugs like ipilimumab, called checkpoint blockade inhibitors, help immune cells to look past cancer’s disguise and target abnormally growing tumors.
In the study, those who received the combination of ipilimumab and sargramostim, another drug that gives the immune system a laser-like focus on the proteins found on tumors, survived an average of 17.5 months after the study began, compared to 12.7 months for those who took ipilimumab alone. At the end of a year, nearly 70% of those receiving the combination were alive, while 53% of those in the ipilimumab alone group were.
“We show that the combination improves survival, and at the same time decreases side effects,” says Hodi. The patients receiving the two drugs reported fewer gut and respiratory complications, two of the organ systems most affected by checkpoint inhibitor drugs like ipilimumab.

Scalability and cost,Pfizer's reason for different approach

“We would like to take it to the next level, where CAR therapies become a more standardized, highly controlled treatment,” said Mikael Dolsten, Pfizer’s head of global research and development.

Working with French biotech Cellectis SA, ALCLS.FR -2.65% Pfizer wants to develop a generic CAR therapy for use in any patient, potentially lowering its cost. But its research is still preclinical, and may not work in humans.

Stephen McGarry, global head of health-care research at Société Générale, agrees the treatments being developed by Novartis and Juno could justify “astronomical” prices, although he thinks health-care payers and patients might fight back.

“When you look at the initial data with the Novartis therapy, you’re getting cures in some kids—what do you charge for that?” he asks

Juno-backed Sloan-Kettering trial, recruiting patients!

There are still big unanswered questions about CAR therapies: one is how long they last.

That is hard to tell because of the small numbers of patients treated so far, and because many of those whose cancer went into remission after the CAR therapies subsequently became eligible for stem-cell transplants which can themselves prolong survival.

Another concern is a potentially dangerous side effect called “cytokine-release syndrome,” an immune response which shows the therapy is working, but which can cause a sharp drop in blood pressure and surge in the heart rate.

The deaths of two patients in a Juno-backed Sloan-Kettering trial in March caused a temporary halt in the study because of worries over these immune responses.

“Patients need to be healthy enough to combat that side effect,” says Mr. Bishop, who thinks it is now manageable. The trial is recruiting patients again, excluding those with a risk of heart failure, and giving those with very advanced leukemia fewer modified cells.

New Costly Cancer Treatments Face Hurdles Getting to Patients

But the biggest hurdle yet may be the cost of the therapies.

The genetic engineering involved means CAR therapies are very complex to manufacture, and each is a unique personalized treatment using a patient’s own blood cells. The inability to mass-produce them has likely implications for how much companies will charge for them.

“What we’re talking about here is a single, very expensive therapy that’s used once for a specific patient and is not generalizable,” says Dr. Malcolm Brenner, director of the Center for Cell and Gene Therapy at the Texas Children’s Hospital in Houston.

Dr. Brenner signed a deal in March to commercialize his own CAR research with Celgene.

Novartis and Juno say it is too early to speculate on price, although Dr. Usman agrees the challenge is getting the manufacturing process to “a viable level where it’s both affordable and attractive.”

While most analysts think it is too early to estimate potential revenue or price, Citigroup believes CAR therapies could cost in excess of $500,000 per patient, which it notes is roughly in line with the cost of a stem cell transplant.

“This technology needs to be widely developed and accessible to patients,” says Dr. DeAngelo. “If the cost is going to be a hindrance, it’s going to be a really sad day.”

Novartis, Juno Conduct New Studies on Leukemia Therapies

Cancer treatments that genetically modify patients’ blood cells to target the disease have shown amazing results in clinical trials. Now drug companies and biotechs must overcome big hurdles to get them into hospitals, including their potential cost.

In two separate clinical trials—sponsored by Novartis AG NOVN.VX -0.51% of Switzerland and Seattle-based biotech Juno Therapeutics Inc.—almost 90% of patients saw their leukemia disappear after being given experimental so-called CAR T-cell therapies. The results were published in December and February, respectively.

Both trials were in small numbers of patients: 22 children in the Novartis trial and 16 adults in the Juno trial. The patients had acute lymphoblastic leukemia—the most common childhood cancer—and had exhausted standard treatments. Both companies are now conducting larger trials.

“CAR T cells are probably one of the most exciting concepts and fields to come out in cancer in a very, very long time,” says Dr. Daniel DeAngelo, a Boston-based hematologist and associate professor of medicine at Harvard Medical School, who wasn’t involved in either study.

Usman Azam, head of cell and gene therapies at Novartis, calls the therapies “critically important” for Novartis. “I think that a cure for cancers such as leukemia and lymphoma through a CAR technology is plausible,” said Dr. Azam in an interview with The Wall Street Journal. “Our job is to get this into patients as soon as we feasibly can.”

New cancer treatment which reprograms cells to self-destruct gives hope for lung patients

A new treatment for cancer which kills cancerous cells and leaves healthy ones untouched could revolutionise treatment, scientists have claimed.
Unlike healthy cells, which eventually self destruct once no longer useful, cancer cells dodge this suicide path.
Instead the cells grow out of control, causing tumours to form.
The scientists, based at the UCL Cancer Institute, believe they have fixed this fault in lung cancer cells, by reprogramming the cells to self destruct.
Through using lung cancer cells and mice, the scientists showed that the combination of two drugs, TRAIL and a CDK9 inhibitor, changed the molecular modifications in the cell suicide process, forcing the cancer cells to self-destruct.
This new drug combination, which will be presented at the National Cancer Research Institute (NCRI) Cancer Conference in Liverpool next week, could pave the way for new treatments.
However the researchers stressed that the drug combination is in early stage development, to potentially treat non small cell lung cancer.
Nell Barrie, senior science information manager at Cancer Research UK, added: "This important research builds on the progress we've made to understand the routes cancer cells use to stay alive.
"Understanding and targeting these processes will move us closer to our goal of three out of four people beating cancer within the next 20 years.
"There's an urgent need to save more lives from lung cancer and we hope these findings will one day lead to effective new treatments to help lung cancer patients and potentially those with other cancer types too."

Breast Cancer and Chemotherapy

When it comes to responding to chemotherapy, not all breast cancers are created equal. So far, doctors have not been able to accurately predict which women would derive added benefits from chemotherapy and which ones wouldn't. So the policy has often been, "When in doubt, get chemotherapy."

Now, studies show that a new genetic test, known as the Oncotype DX 21-gene assay, not only assesses the likelihood of breast cancer recurrence for many early-stage breast cancer patients, but also predicts how much chemotherapy will help these women. This new test may give some low-risk women the option of skipping the rigors of chemotherapy, while reassuring others that the often-difficult treatment they're receiving has a clearly defined benefit.

For women who have hormone-positive breast cancer that has not yet spread to the lymph nodes, the Oncotype assay analyzes 21 genes related to breast cancer in the body that breast cancer cells depend on, including the estrogen receptor, HER2 and proliferation genes. It then divides the results into low-, medium-, and high-risk scores.

Women in the low-risk group, about half the patients studied, would get only a minimal, if any, benefit from chemotherapy. Women in the high-risk group would be very likely to benefit from chemotherapy.

Herceptin Clinical Trials for Breast Cancer

Four large-scale, randomized clinical trials are now under way to better identify the benefits and risks of Herceptin. "It's very likely that Herceptin will be an effective therapy in early-stage disease, based on what we've seen in metastatic breast cancer," says Sloan-Kettering's Hudis. "But what's not so clear yet is how big an impact it will have on survival and recurrence rates, and what the price might be for a broad population in terms of heart failure. If we improve survival rates by 2%, but it causes 4% of patients to have significant heart failure, then you'd have a hard time figuring out what to do next."

In the small group of study patients at M.D. Anderson who received Herceptin, says Buzdar, none so far has developed any heart problems almost two years after treatment. Some doctors have prescribed Herceptin "off-label" for women with non-metastatic breast cancer, but both Hudis and Isaacs are cautious. They recommend women with early-stage breast cancer only take Herceptin if they are in a clinical trial until more questions are answered about the drug's risks and benefits.

Herceptin in the Treatment for Breast Cancer

For several years, the drug Herceptin has been used to treat women with HER2-positive breast cancer that has metastasized or recurred. It's a kind of drug known as a monoclonal antibody. It works like a heat-seeking missile, homing in on cells that make too much HER2neu protein. Used either with chemotherapy or alone, Herceptin can reduce tumor size and increase a woman's chances of both overall survival and disease-free survival.

But the trials that led to Herceptin's FDA approval were all in women with advanced breast cancer. Would Herceptin work as well in women with early-stage disease? Within the last year, promising research has indicates the answer may be yes.

In a study released last June, scientists at the University of Texas M.D. Anderson Cancer Center in Houston looked at women with early-stage, HER2-positive breast disease. They found that more than twice as many women who received Herceptin as part of their presurgical chemotherapy had their tumors completely disappear compared with women who received chemotherapy alone. Indeed, the results were so striking that the researchers stopped the study early, after enrolling only 42 of a planned 164 patients.

"More than 65% of the Herceptin patients had a complete response rate, as compared with only 26% of patients who received chemotherapy only," says Aman Buzdar, MD, deputy chair of the department of breast and medical oncology at the M.D. Anderson Cancer Center.

So why hasn't Herceptin been approved for use in early-stage HER2-positive breast cancer yet? First, because of the relatively small size of the trial, and second, because of concerns about its side effects. In a small percentage of patients, Herceptin can cause heart damage and sometimes even heart failure.

Aromatase Inhibitors

Aromatase inhibitors aren't new. The FDA approved the first, Arimidex, in September 2000. Many large trials have recently confirmed that these hormone therapies outperform the more commonly used tamoxifen to prevent tumor recurrence in women who had hormone-positive breast cancers (cancers that are fed by estrogen).

Because they act only on estrogen that's produced outside the ovaries, aromatase inhibitors are only effective in postmenopausal women. (Before menopause, most of the body's estrogen is produced in the ovaries.) But for these women, Arimidex and its sister drugs, like Aromasin and Femara, offer a small but crucial advantage over tamoxifen -- 4% to 5% -- in preventing cancer recurrence. Researchers still don't know which strategy works best: taking an aromatase inhibitor instead of tamoxifen, as the first course of therapy after surgery for breast cancer (called adjuvant therapy) or beginning treatment with tamoxifen and switching to an aromatase inhibitor after two to five years.

Other factors involved with Abraxane

Another factor could be involved. Because albumin, which normally transports nutrients to cells, accumulates in rapidly growing tumors, it's possible that the bundles of Abraxane in their albumin "envelopes" are sent by express delivery directly to cancer cells. "There are signs indicating that albumin receptors in breast cancer and other cancer cells would preferentially pick up these albumin-bound packets."

If so, that may have exciting implications for other chemotherapy drugs used in breast and other cancers, says Claudine Isaacs, MD, director of the Clinical Breast Cancer Program at the Lombardi Comprehensive Cancer Center at Georgetown University Medical Center in Washington, D.C. "This delivery system probably will not be limited to paclitaxel. Theoretically, you could put any number of chemotherapy drugs in these packets, not just paclitaxel." And years of experience with chemotherapy show that delivery matters. "The same drug can have a very different side effect profile, as well as potentially different benefits and response rates, based on how it's delivered."

So far, Abraxane has only been FDA-approved for use in patients with breast cancer that has recurred or metastasized. Still, many drugs that are first approved for use in this stage of the disease later prove to be effective for women with earlier-stage breast cancer.

New Treatments for Breast Cancer

Paclitaxel, commonly marketed as Taxol or Taxotere, is part of many chemotherapy drug regimens, but it has one big problem, says Clifford Hudis, chief of the Breast Cancer Medicine Service at New York's Memorial Sloan-Kettering Cancer Center. "It doesn't dissolve in water, which means we have to put the drugs in solvents to deliver them to patients." Those solvents can cause a number of side effects, including severe allergic reactions. Patients taking paclitaxel have to receive heavy doses of other medications first, such as steroids and antihistamines, before getting their chemotherapy.

Abraxane does a neat end run around that problem. A process called protein-bound nanoparticle technology creates tiny particles that bind the paclitaxel to a naturally occurring protein called albumin. "The binding makes little packets of paclitaxel, think of them as little bubbles, that can be dissolved in water," says Hudis. This means no more solvent, which in turn means no more medications before chemotherapy, and no more of the side effects that go along with them. It's also shortened the chemotherapy's infusion time from more than three hours to around half an hour.

These practical pluses would be enough to make anyone receiving chemotherapy rejoice. But there may also be a bonus in terms of the drug's effectiveness. In one of the major clinical trials that led to Abraxane's FDA approval, women who got this drug had almost twice the response rate to chemotherapy compared with women who received regular Taxol. This may be in part because without the need for solvents, higher doses of paclitaxel could be delivered to the women getting Abraxane.

New Iridium- based Drug for Chemo Therapies

"Platinum-based drugs are used in nearly 50% of all chemotherapeutic regimens, exert their activity by damaging DNA and cannot select between cancerous and non-cancerous cells, leading to a wide-range of side-effects from renal failure to neurotoxicity, ototoxicity, nausea and vomiting.
"In contrast, the new iridium-based drug is specifically designed not to attack DNA, but to have a novel mechanism of action, meaning that it could not only dramatically slow down and halt cancer growth, but also significantly reduce the side effects suffered by patients" argues Professor Sadler.
This research could also lead to substantial improvements in cancer survival rates. "Current statistics indicate that one in every three people will develop some kind of cancer during their life time, moreover approximately one woman dies of ovarian cancer every two hours in the UK according to Cancer Research UK .It is clear that a new generation of drugs is necessary to save more lives and our research points to a highly effective way of defeating cancerous cells" said Dr Romero-Canelon.

Cancer treatment revolution potential with new drug

A new study at the University of Warwick, published in the journal Angewandte Chemie International Edition, has developed a new drug that can manipulate the body's natural signalling and energy systems, allowing the body to attack and shut down cancerous cells.
Called ZL105, the drug is a compound based on the precious metal iridium. The study has found ZL105 could potentially replace currently used anticancer drugs, which become less effective over time, cause a wide-range of side-effects and damage healthy cells as well as cancerous.
Commenting on the breakthrough, University of Warwick researcher and study co-author Dr Isolda Romero-Canelon said "The energy-producing machinery in cancer cells works to the limit as it attempts to keep up with quick proliferation and invasion. This makes cancer cells susceptible to minor changes in the cell 'power-house'. Our drug pushes cancer cells over the limit causing them to slow and shut down, whilst normal cells can cope with its effects."
Preliminary data indicate that the novel drug may be ten times more effective in treating ovarian, colon, melanoma, renal, and some breast cancers, according to data obtained by the US National Cancer Institute. The researchers now aim to expand the study to cancers that are inherently resistant to existing drugs and to those which have developed resistance after a first round of chemotherapy treatments.
Study co-author Professor Peter J. Sadler said "Existing cancer treatments often become less effective after the first course, as cancer cells learn how they are being attacked. The drug we have developed is a catalyst and is active at low doses. It can attack cancer cells in multiple ways at the same time, so the cancer is less able to adapt to the treatment. This means the new drugs could be much more effective than existing treatments."

Novartis, Juno Conduct New Studies on Leukemia Therapies

“CAR T cells are probably one of the most exciting concepts and fields to come out in cancer in a very, very long time,” says Dr. Daniel DeAngelo, a Boston-based hematologist and associate professor of medicine at Harvard Medical School.

Usman Azam, head of cell and gene therapies at Novartis, calls the therapies “critically important” for Novartis. “I think that a cure for cancers such as leukemia and lymphoma through a CAR technology is plausible,” said Dr. Azam . “Our job is to get this into patients as soon as we feasibly can.”

Dr. Azam heads a new unit Novartis created partly to speed the therapies’ time to market. Its leading CAR therapy was granted ‘breakthrough’ designation by the U.S. Food and Drug Administration in July, and Novartis wants to file it with regulators in 2016.

CAR therapies are a mixture of genetic tweaking and “immunotherapy,” or using the patient’s own immune system to fight disease. They involve extracting disease-fighting white blood cells called T-cells from a patient’s blood. The T-cells are then genetically modified, grown in a laboratory for around 10 days and reinjected into the patient.

Typically, the T-cells are combined with a disabled virus, which enables them to produce chimeric antigen receptors, or CARs, that recognize and target malignant proteins on a cancer cell’s surface.

Novartis and Juno are developing their treatments in partnership with top academic teams: Novartis with the University of Pennsylvania and Juno with teams at Memorial Sloan-Kettering Cancer Center in New York, Seattle Children’s Hospital and the Fred Hutchinson Cancer Research Center, also in Seattle.

Doctors Excited by New Cancer Treatment

“Molecularly Targeted Therapy.” The treatment consists of drugs designed at the molecular level of the cell to specifically attack and kill only the cancer cells of a specific type of cancer. And they are tailor-made to recognize specific molecules unique to specific cancers.

The model drug leading the way is Glivec, also known as STI571. It is active against a relatively rare form of leukemia, chronic myeloid leukemia, or CML characterized by excessive overproduction of white blood cells. Approximately 7,000 Americans are diagnosed with CML each year.

Doctors are extremely hopeful that the drug could provide a model for similar drugs to treat cancers affecting many thousands more people. This year, alone, some 1.3 million Americans will be diagnosed with cancer.

“This is as important as it gets. A cancer-specific target, a drug specifically designed for the target, the most effective agent ever,”says Paul A. Bunn Jr., president-elect of the American Society of Clinical Oncology. “Read my lips, this is real, not mice.”

Dr. Brian Druker, director of the Leukemia Program at the Oregon Health Sciences University in Portland, is the main researcher on the drug, which is being developed by Novartis Pharmaceuticals.

Merck’s New Drug Seen As Breakthrough in Cancer Treatment

WEST POINT, Pa. (CBS) — Area oncologists are hailing the FDA’s approval of a new cancer drug developed by Merck, which has a large facility in Montgomery County.
The drug, a new form of immuno-therapy is called Keytruda.  And it’s being called a game changer in the field of cancer treatment.
The drug has been approved for use against melanoma, but Dr. Hossein Borghaei, of Fox Chase Cancer Center, says similar treatments are being developed to control other forms of cancer.
“We now have at least preliminary report that immuno-therapy can be very effective in lung cancer,”   “There are many different companies working on developing drugs that, in essence, are thought of as taking the brake off the immune system, to allow the patients own immune system to recognize the tumor as foreign and to try to control the disease that way.”
Bristol Myers expects to file for FDA approval of its new drug to treat melanoma by the end of the month.

Bone marrow transplants

A bone marrow transplant is a procedure to replace damaged or destroyed bone marrow with healthy bone marrow stem cells.
Bone marrow is the soft, fatty tissue inside your bones. Stem cells are immature cells in the bone marrow that give rise to all of your blood cellsThere are three kinds of bone marrow transplants:

• Autologous bone marrow transplant: The term auto means self. Stem cells are removed from you before you receive high-dose chemotherapy or radiation treatment. The stem cells are stored in a freezer (cryopreservation). After high-dose chemotherapy or radiation treatments, your stems cells are put back in your body to make (regenerate) normal blood cells. This is called a rescue transplant.
• Allogeneic bone marrow transplant: The term allo means other. Stem cells are removed from another person, called a donor. Most times, the donor's genes must at least partly match your genes. Special blood tests are done to see if a donor is a good match for you. A brother or sister is most likely to be a good match. Sometimes parents, children, and other relatives are good matches. Donors who are not related to you may be found through national bone marrow registries.
• Umbilical cord blood transplant: This is a type of allogeneic transplant. Stem cells are removed from a newborn baby's umbilical cord right after birth. The stem cells are frozen and stored until they are needed for a transplant. Umbilical cord blood cells are very immature so there is less of a need for matching. But blood counts take much longer to recover.

What causes swollen glands?

The most common causes of swollen glands include:

• Bacterial infection, such as strep throat.
• Mouth sores or tooth infection.
• Viral infection, such as mononucleosis  or "mono."
• Skin infection.
• Ear infection.
• Sexually transmitted disease.
• Cancers such as leukemia, Hodgkin's disease, non-Hodgkin's lymphoma, and breast cancer.
• Immune system disorders, such as lupus, rheumatoid arthritis, and HIV infection.
• Side effect from a vaccine or from certain medications.

What increases the risk of getting Non-Hodgkins Lymphoma?

No one knows exactly what increases your risk of getting non-Hodgkin's lymphoma (NHL). Experts do agree that the disease is not caused by injury and is not contagious. The following risk factors may increase your chances of having the disease. But most people with these risk factors do not ever have non-Hodgkin's lymphoma, and many people who have non-Hodgkin's lymphoma do not have any of these risk factors.²

• Being male. NHL is more common in men than in women.
• Age. The likelihood of getting NHL increases as you get older.
• Impaired immune system. NHL is most common among those who have an impaired immune system, an autoimmune disease, or HIV or AIDS. It also occurs among those who take immunosuppressant medicines, such as medicines following an organ transplant.
• Viral infection. A viral infection, such as Epstein-Barr virus, increases the risk of developing NHL.
• Bacterial infection. Infection with Helicobacter pyloriincreases the risk of lymphoma involving the stomach.
• Environmental exposure. Exposure to agricultural pesticides or fertilizers, solvents and other chemicals, rubber processing, asbestos, and arsenic increases the risk of developing NHL.

The survival rate and prognosis for Hodgkin's Lymphoma

The five-year survival rate refers to the percentage of patients, according to the stage of their disease at diagnosis, who live at least five years after treatment for Hodgkin lymphoma. Many of these patients live longer than five years.

• Stage I: 90%-95%
• Stage II: 90%-95%
• Stage III: 85%-90%
• Stage IV: about 80%

Long-term health problems can occur after treatment of Hodgkin lymphoma that are related to the treatment -- leukemia, myelodysplastic syndromes, breast cancer, heart disease, thyroid disease, lung disease, including lung cancer, and infertility. Annual physical exams are essential to screen for other diseases. Tests might include annual breast MRI scans and/.or annual chest CT scans. Medical  attention should be sought, promptly, for any new, serious symptoms.

What happens to a person with Non-Hodgkin's Lymphoma

In non-Hodgkin's lymphoma (NHL), either abnormal cells in the lymphatic system divide and grow without order or control or old cells do not die normally. Lymphatic tissue is present in many areas of the body, so non-Hodgkin's lymphoma can start almost anywhere in the body.
Non-Hodgkin's lymphoma may occur in a single lymph node, a group of lymph nodes, or an organ. And it can spread to almost any part of the body, including the liver, bone marrow, and spleen. Doctors classify NHL into stages based on where the lymphoma is growing in the body.
Over time, lymphoma cells may replace the normal cells in the bone marrow. Bone marrow failure results in the inability to produce red blood cells that carry oxygen, white blood cells that fight infection, and platelets that stop bleeding.
Long-term survival depends on the type of non-Hodgkin's lymphoma and the stage of the disease when it is diagnosed. Approximately 81 out of 100 people diagnosed with non-Hodgkin's lymphoma are alive 1 year after the disease is diagnosed. That number drops to about 63 out of 100 at 5 years and 49 out of 100 at 10 years.

Knowing if I have Hodgkin's Lymphoma

The diagnosis of Hodgkin lymphoma can only be made by a tissue biopsy -- cutting a tissue sample for examination. If you have an enlarged, painless lymph node that your doctor suspects may be due to Hodgkin lymphoma, tissue will be taken for biopsy or the entire node will be removed. The diagnosis of Hodgkin lymphoma can be confirmed if a type of cell, called a Reed-Sternberg cell, is seen.

If a biopsy reveals that you do have Hodgkin lymphoma, you may need additional tests to determine the extent, or stage, of the disease. Tests include blood tests, chest X-ray, computed tomography (CT) scans of the chest, abdomen and pelvis, and possibly the neck, and a PET scans. Magnetic resonance imaging (MRI) scans, bone scans, spinal tap (lumbar puncture), and bone marrow studies are useful under special circumstances.
These tests will confirm the stage of the disease and the best type of therapy to pursue. 

Other Non-Hodgkin Lymphoma risk factors

• Chemical exposure:  arsenic, lead, vinyl chloride, asbestos, insecticides, pesticides and weed killers, wood preservatives, organic chemicals, and solvents
• Exposure to nuclear accidents,  nuclear testing, or underground radiation leaks
• Treatment with immunosuppressant drugs, for prevention of organ transplantation rejection, or for treatment of inflamatory and autoimmune disorders
• Tumor necrosis factor agents used to treat psoriatic and rheumatoid arthritis and inflammatory bowel disease
• Prior exposure to chemotherapy and/or radiation used to treat a prior diagnosis of  cancer
• Treatment with a medication called Dilantin (phenytoin), commonly used to treat seizure disorders
• Use of hair dyes, especially dark and permanent colors, used before 1980
• High levels of nitrates found in drinking water
• Diets high in fat and meat products
• Ultraviolet light exposure
• Alcohol intake

What causes Non-Hodgkin's Lymphoma?

The exact cause of non-Hodgkin lymphoma is unknown. However, there are multiple medical conditions that are associated with an increased risk of developing non-Hodgkin lymphoma:

• Inherited immune deficiencies: ataxia-telangectasia, Wiskott-Aldrich syndrome, common variable immunodeficiency, severe combined immunodeficiency, and X-linked lymphoproliferative syndrome
• Genetic syndromes: Down syndrome, Klinefelter's syndrome (a genetic condition in men caused by an extra X chromosome)
• Immune disorders, and their treatments: Sjögren's syndrome (an immune disorder characterized by unusual dryness of mucus membranes), rheumatoid arthritis, systemic lupus erythematosus
• Celiac disease, a disease involving the  processing of certain components of gluten, a protein in grains
• Inflammatory bowel disease, particularly Crohn’s disease, and its treatment
• Psoriasis
• Family history of lymphoma
• Bacteria: Helicobacter pylori, asssociated with gastritis and gastric ulcers; Borrelia burgdorferi, associated with Lyme disease; Campylobacter jejuni; Chalmydia psittaci
• Viruses: HIV, HTLV-1, SV-40, HHV-8, Epstein Barr virus, hepatitis virus
• Non-random chromosomal translocations and molecular rearrangements