A new type of drug that releases the immune system against tumors has been remarkably successful, but only for certain cancer patients. Researchers have found a genetic signature in lung tumors that seems to predict if this immunotherapy drug will work and who will benefit most.
Tumor cells can hide from the immune system by activating a receptor called PD-1 on the surface of immune cells called T cells Instead of attacking tumor cells, T cells leave alone. The new drug is an antibody that inhibits PD-1 blocking this "checkpoint" and release the T cells to remove tumor cells. In clinical trials, PD-1 blockers and other checkpoint inhibitors have prolonged the lives of patients with several types of cancer for years, much longer than conventional treatments. The US Food and Drug Administration has approved several of these drugs for melanoma and one of them, nivolumab, became the first to win approval for lung cancer last week. But the checkpoint inhibitors only work for some people inhibitors-PD-1 shrink tumors in about 20% to 30% of patients and lung cancer researchers are scrambling to figure out why.
One hypothesis is that the checkpoint inhibitors are more likely to work on tumors with more mutations. These mutations are not necessarily those that allow tumor cells to divide uncontrollably or spread to other locations; instead, they can simply encode abnormal proteins that do nothing to the cancer cell. But they can importance for immunotherapies because aberrant molecules may act as foreign-antigens molecules in the body that trigger an immune response. The more mutations in the tumor of a patient, most of these so-called neoantigens and therefore a stronger T cell response in patients taking a checkpoint inhibitor, the thinking goes.
Recent studies support this view. the melanoma patients with more mutations in their tumors neoantigen encoding, for example, were more likely to respond to a checkpoint inhibitor which blocks a protein called CTLA-4.
Now the same seems true for lung cancer. Timothy Chan of Memorial Sloan Kettering Cancer Center in New York, who led the melanoma study, and his colleagues sequenced the exome-protein-encoding DNA-tumors of 34 people with lung cancer non-small cell that had been treated with a PD-1 inhibitor called pembrolizumab. They found that patients were more likely to respond to the drug if the tumor was more the type of mutation which leads to a modified protein. For example, 13 of 18 (72%) patients with at least 178 mutations responded for 6 months or more, compared with one of 13 (8%) of those with fewer mutations. In addition, cancer patients 16 lung that had a distinctive pattern of mutations caused by smoking were more likely to respond that the alleged non-smokers, who had less, different mutations, the group of Chan reports online aujourd 'hui in Science .
the correlation between mutations and therapeutic response to drugs against cancer is "eye-popping" says cancer researcher Drew Pardoll Johns University School Hopkins of Medicine in Baltimore, Maryland, which does was not involved in the study but has worked with the group of Chan. "It is a very important result." Although the results do not necessarily mean that all non-smokers do not respond to PD-1 blockers, DNA sequencing of tumor biopsies could help oncologists decide which drug to give first, he and Chan say. and he suggests that these drugs may work on other smoking-related cancers, such as esophageal cancer and head and neck, Chan added.
the researchers are also studying the possibility of giving patients a personalized vaccine made from neoantigens in their tumor to enhance their response to a checkpoint inhibitor. "I think the potential is huge," said Roy Herbst, a cancer researcher lung at Yale University.
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