Discovery About How Cancer Cells Evade Immune Defenses Inspires New Treatment Approach; Inhibiting Action of Scissor-Like ENPP1 Protein May Strike at Cancer in Two Different Ways, Sloan-Kettering Study Indicates

Cancer cells are known for spreading genetic chaos. As cancer cells divide, DNA segments and even whole chromosomes can be duplicated, mutated, or lost altogether. This is called chromosomal instability, and scientists at Memorial Sloan Kettering Cancer Center (MSKCC) have learned that it is associated with cancer's aggressiveness. The more unstable chromosomes are, the more likely that bits of DNA from these chromosomes will end up where they don't belong: outside of a cell's central nucleus and floating in the cytoplasm. Cells interpret these rogue bits of DNA as evidence of viral invaders, which sets off their internal alarm bells and leads to inflammation. Immune cells travel to the site of the tumor and churn out defensive chemicals. A mystery has been why this immune reaction, triggered by the cancer cells, does not spell their downfall. "The elephant in the room is that we didn't really understand how cancer cells were able to survive and thrive in this inflammatory environment," says Samuel Bakhoum (https://www.mskcc.org/research-areas/labs/samuel-bakhoum),MD, PhD, a physician-scientist at MSKCC and a member of the Human Oncology and Pathogenesis Program. According to a new study from Dr. Bakhoum's lab, published online on December 28, 2020 in Cancer Discovery (https://cancerdiscovery.aacrjournals.org/content/early/2020/12/23/2159-8290.CD-20-0387), the reason has to do, in part, with a molecule sitting on the outside of the cancer cells that destroys the warning signals before they ever reach neighboring immune cells. The findings help to explain why some tumors do not respond to immunotherapy, and--equally important--suggest ways to sensitize them to immunotherapy. The warning system Dr. Bakhoum studies is called cGAS-STING.
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