The most promising Cancer Therapy in Decades

As cancers develop, they also evolve and diversify. Cells on one side of a tumor can end up with very different mutations (and neoantigens) from those just centimeters away. This concept, known as ‘heterogeneity,’ partly explains why the war against cancer has been so entrenched. Consider the much-vaunted “targeted therapies”, drugs that go after mutations specific to a patient’s cancer. If those mutations are found only in some parts of a tumor, the treatment will leave a reservoir of cells that can grow anew, or even evolve resistance to the drug. That’s why many people get great results with targeted therapies, but then rebound within a few months.
Heterogeneity matters to the immune system, too. Some mutations develop early on in a tumor’s life and are found in all of its cells. Let’s call them trunk mutations. Others are latecomers and found in just a fraction of the tumor cells. Those are the branches.
Quezada and Swanton’s teams found that patients had better survival rates if their tumors have lots of trunk neonatigens, but not branch ones. They also responded better to pembrolizumab, one of those checkpoint inhibitors that works by unleashing the immune system (and the drug Jimmy Carter recently took). The team studied 34 patients and found that almost everyone whose tumors had a wide trunk and sparse branches responded well to the drug. By contrast, the poorest responders almost all had thin trunks and luxuriant branches. They found the same pattern among 64 melanoma patients treated with two different drugs.“This is the first evidence that there are seeds of a tumor’s own destruction nestling in the tumor itself,” says Swanton.“We need to work out how to activate these T-cells.”“We’re not naïve,” says Swanton. “We know there is a long way to go. This is the first step in an exciting journey.”