New type of Cancer Treatment targets proteins in Cancer Cells

A new therapeutic approach that targets an aggressive form of lymphoma may greatly increase the efficacy of treatment and result in better outcomes for patients, according to new research by scientists at Weill Cornell Medicine.
Diffuse large B-cell lymphoma (DLBCL) is an aggressive cancer of the B-cells, a type of white blood cell. It is the most common form of non-Hodgkin lymphoma, affecting approximately 20,000 Americans each year. Current therapies are ineffective for at least 40 percent of patients with DLBCL and come with severe side effects ranging from fever and nausea to heart and nerve damage.
Drs. Goldstein and Melnick and their team focused on proteins that exist in all cells. In particular, they looked at one protein called Hsp90, which acts like a scaffolding for other proteins in the cells. Cancer cells hijack this scaffolding function to stabilize the mutant proteins they require for survival.
"If we could identify the proteins that Hsp90 is stabilizing in these cells," Dr. Goldstein said, "then we might be able to therapeutically target them in combination with Hsp90 inhibition."
The researchers used an experimental drug developed at Memorial Sloan Kettering called PU-H71, which binds to Hsp90 to trap it in a complex with the other proteins it stabilizes, known as client proteins. With this method, they identified client proteins that are critical to lymphoma survival and can be targeted therapeutically. They then treated lymphoma cells in petri dishes, mice, and human tumor samples with PU-H71 and ibrutinib, a drug that is used to treat lymphoma that targets one of the major lymphoma survival pathways identified. Every time, the drug combination proved to be more effective at killing lymphoma cells than ibrutinib or PU-H71 alone.