Loss of Certain Protein Identified in Ovarian Cancer Resistance to PARP Inhibitors

Loss of Certain Protein Identified in Ovarian Cancer Resistance to PARP Inhibitors
Researchers have identified a mechanism of resistance to PARP inhibitors — such as Lynparza (olaparib) and — in ovarian cancer, that involves the loss of a specific protein called 53BP1, according to a recent study. This finding may help physicians predict which cancer patients are more likely to develop a resistance to PARP inhibitors — based on the levels of 53BP1's function — and to decide the best possible treatment. The study, “53BP1–RIF1–shieldin counteracts DSB resection through CST- and Polα-dependent fill-in,” was published in the journal Nature, and is the result of a collaboration between researchers in the U.S., United Kingdom, Canada, and Sweden. Mutations in the BRCA tumor suppressor genes are responsible for 5.8% to 24.8% of all ovarian cancer cases, and women carrying these mutations are estimated to have a 44% chance of developing ovarian cancer by the age of 80. These mutations cause defects in a major DNA repair mechanism that repairs cuts on both strands of DNA, allowing the replication of genetic errors and facilitating the development of cancer. To survive, these cancer cells rely on another repair mechanism, based on an enzyme called PARP1. Researchers have taking advantage of that situation by developing PARP inhibitors — molecules that suppress PARP1 function — potentially leading to the accumulation of DNA damage, and ultimately to the death of these cancer cells. However,
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