Genetic Biomarker May Predict Cancer Patients’ Response to Immunotherapy
Biological changes that knock out genes involved in the repair of damaged DNA might predict who will respond to certain immunotherapy drugs, according to data from a proof-of-principle study co-authored by scientists at the OSUCCC – James.
The finding comes from a phase II trial examining the effectiveness of the immunotherapy drug pembrolizumab (marketed as Keytruda). Richard Goldberg, MD, physician-in-chief at the OSUCCC – James, serves as principal investigator of the local arm of this clinical trial and co-author of the study. Luis Diaz Jr., MD, of Johns Hopkins Kimmel Cancer Center, is principal investigator of the national trial.
Defects in mismatch repair genes were originally discovered in 1993 by a team that included Albert de la Chapelle, MD, PhD, who is now in the Molecular Biology and Cancer Genetics Program at the OSUCCC – James. Defects, or mutations, in mismatch repair genes occur in both sporadic and hereditary forms of colorectal, endometrial, stomach, biliary tract, pancreatic, ovarian and small intestine cancer. The mutations disable a cell’s ability to repair small errors in its DNA. Loss of this repair mechanism leads to unchecked cellular growth.
The study suggests that patients with mutations in mismatch repair genes respond better to pembrolizumab than patients with normal mismatch repair genes.
“This study is a real-life example of how gene sequencing of tumor cells and precision cancer medicine can improve our approach to treating cancers with immunotherapy agents based on a cancer’s genetic signature, rather than on the class of cells or the organ in which the tumor occurs,” Goldberg says.
Published in the New England Journal of Medicine.
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