Some gastric tumors have genetic abnormalities that can be directly targeted with drugs, such as HER2 mutations. But cancer is a complex disease that’s also governed by “epigenetics,” the process in which DNA is altered in a way that affects gene expression.
The Foundation has awarded $75,000 to the lab of Heinz-Josef Lenz, professor of medicine, Associate Director Clinical Science and co-director of the USC Norris Center for Cancer Drug Development. Lenz’s lab will use the funding to investigate epigenetic changes in gastric cancer—and potential treatment pathways that address them.
“We know that the cancer genome can be regulated by mutations, but we also know that genes can be silenced” by epigenetic forces including histone modifications, Lenz says. “It’s important to understand these critical processes, because it could identify new targets for drug development.”
Lenz’s team will use the grant to build upon previous discoveries related to KMT2, a gene that, when altered, has been associated with more advanced cases of gastric cancer and poor survival. The researchers analyzed tumors from 1,245 patients with advanced gastric cancer and discovered that high mutation rates in KMT2 often correlated with changes in other genes related to DNA damage repair and chromatin remodeling, both of which can drive tumor growth and progression.
The Gastric Cancer Foundation grant will help fund the next phase of the research plan, which is to test drugs and combination treatments, in the hopes of finding more effective therapies for gastric tumors carrying KMT2 alterations. Lenz and his colleagues are interested in testing PARP inhibitors in animal models of gastric cancer. These drugs, many of which are already FDA approved to treat other cancers, are designed to inhibit DNA repair in cancer cells, which in turn promotes the death of the cells.
They also plan to investigate novel drugs, one of which inhibits ATR, a protein kinase that is also involved in DNA repair.
Finding new treatments for gastric cancer is a priority of USC, Lenz says. “Gastric cancer is one of our major diseases in our cancer center catchment area, where there’s a significant Asian and Hispanic population. That really inspires us to find more and better treatment options.”
And the funding from The Gastric Cancer Foundation is a critical step towards advancing the understanding of epigenetics and histone modifications in gastric cancer, Lenz adds. “Gastric cancer is a bit neglected in the philanthropic world. The Gastric Cancer Foundation is absolutely critical,” Lenz says. “This grant can be the jumpstart for us to generate the data we need to be able to get larger funding from the National Institutes of Health and the National Cancer Institute.”