Treatments that harness the immune system to fight cancer have greatly improved outcomes for some people with cancer. Scientists are learning more about why some people respond much better than others to these drugs.
One major factor is something called tumor mutation burden (TMB) — the number of DNA changes a tumor has. Studies from researchers at Memorial Sloan Kettering and elsewhere have shown that tumors with high TMB tend to respond better to immune checkpoint inhibitors. In 2017, the US Food and Drug Administration approved the checkpoint inhibitor pembrolizumab (Keytruda®) for the treatment of tumors with a type of genetic defect called mismatch repair (MMR) deficiency.
MMR is one of several DNA repair pathways that cells use to fix mistakes in DNA. Mutations in this pathway lead to faulty DNA repair and therefore to higher TMB. Next to MMR, the most commonly mutated DNA repair pathway is called homologous