Could new technology help identify a new role in gastric cancer for a drug that’s been used for the past eight years to treat other cancers? That’s the goal of Gastric Cancer Foundation grant awardee Nilay S. Sethi, M.D., Ph.D., associate program director of the medical oncology fellowship at Dana-Farber/Mass General Brigham and an assistant professor of medicine at Harvard medical school.
The foundation recently awarded Sethi a $100,000 grant to study the potential of a class of targeted drugs called PARP (poly-ADP ribose polymerase) inhibitors to treat some patients with gastric cancer. He was one of two researchers the Foundation chose for the grant award. Eunyoung Choi, Ph.D., assistant professor in the section of surgical science at Vanderbilt University, also won $100,000 to further her research, which is focused on the transformation of precancerous stomach tissue into cancer.
Inhibiting PARP, an enzyme that cancer cells use to repair themselves, causes cancer cells to die, and this therapeutic approach has already proven successful in some women with breast and ovarian cancer and men with prostate cancer. Sethi believes a subset of gastric cancer patients whose tumors are deficient in “homologous recombination” (HR)—another pathway by which cancer cells repair themselves—will respond well to a combination of PARP inhibitors and platinum chemotherapy.
“Research has shown that a substantial amount of gastric cancers have a signature of mutations” suggesting HR repair deficiencies, Sethi says. It’s possible that 25% of patients have defects in this pathway and could therefore respond well to the chemo-PARP inhibitor combination, he adds.
Sethi’s research team will start by sequencing tumor samples from gastric cancer patients who responded well to platimum chemotherapy, as well as from those who did not, in order to determine whether HR deficiencies are more prevalent in responders.
From there, they will use single-cell RNA sequencing technology to investigate what happens when gastric cancer cells that are deficient in HR are treated with PARP inhibitors. “This technology will allow us to see which cells die after treatment, which respond the best and which are insensitive to PARP inhibition,” Sethi says. “This single-cell profiling will really help us understand the response to PARP inhibition.”
With the results, Sethi hopes to apply for a larger government-funded grant. Ultimately he hopes to gather enough data to persuade one of the pharmaceutical companies that makes PARP inhibitors to support a clinical trial in gastric cancer.
Sethi says he’s grateful for the support from Gastric Cancer Foundation. “To receive this grant from a foundation comprised of people who have been affected either directly or indirectly by gastric cancer is really meaningful,” he says. “This is such a challenging cancer to understand, and this funding helps us accelerate progress.”