The FDA’s recent approval of Keytruda could be the start of a golden age of chemotherapy drugs that target the PD-1 pathway. New drugs to treat cancer come along pretty regularly, and, to gain approval, each one must outperform the current standard treatment. But the share of patients who respond to a new drug can be modest, and the months of life they gain by using it are, sadly, often counted in the single digits. Now, there’s hope among researchers and pharmaceutical companies that a drug approved by the Food and Drug Administration (FDA) earlier this month will pave the way toward bigger gains against cancer. The drug, pembrolizumab (Keytruda), is designed to treat melanoma skin cancer, which kills almost 10,000 Americans a year. One in four patients responds to the drug, and many go into a long remission. Keytruda and others still in the FDA approval pipeline disrupt a process by which cancer cells tell the immune system not to attack them as intruders. The drugs are already being tested on kidney, bladder, and small cell lung cancers and could eventually be used against an even wider range of cancers. Related News: Emerging Treatments Offer Hope for Patients with Small Cell Lung Cancer »

PD-1 Is Pretty Darn Hot Keytruda and a handful of other drugs that target the same process are “the hottest area in cancer research,” according to Dr. Antoni Ribas, an expert on cancer immunotherapies at the University of California, Los Angeles. “This is I think the beginning of what will be a fairly significant change in the way that we treat multiple types of cancer in the years and decades to come,” agreed Dr. Evan Lipson, an assistant professor of oncology at the Johns Hopkins University medical school. Scientists have long known that cancer somehow tricks the immune system in order to grow and spread. About 15 years ago, researchers discovered the PD-1 pathway that is the basis of Keytruda and other new drugs. The work built on research on a separate but related pathway that resulted in the drug ipilimumab (Yervoy). Learn More About the Melanoma Drug Yervoy » We can imagine the immune response as like a car at an intersection, looking for a green light telling it to move forward and attack cancer cells, or a red light telling it to remain stopped, Lipson said. There are a series of lights that calibrate the immune system’s response. Cancer cells have devised ways to turn green lights red, escaping the immune system’s attack. (PD-1, a protein on the surface of T-cells, is one potential red light, turned on by PD-1 ligand, or PDL, on the surface of the cancer cells.) Now scientists have learned to turn those lights green again, unleashing the “tremendous power of the immune system,” Lipson said. “This is I think the beginning of what will be a fairly significant change in the way that we treat multiple types of cancer in the years and decades to come.” — Dr. Evan Lipson, Johns Hopkins University



The current optimism comes from observations that green lights on this particular pathway send a lot of cancer-fighting traffic through. And the traffic keeps on coming, so patients remain in remission for longer. “People have tried to activate anti-tumor immunity in the past, but the approach that seems to work well is to block these paths,” said Dr. Arlene Sharpe, an immunologist at Harvard Medical School.