“The ultimate goal of this project is to quickly bring laboratory-tested and verified novel drug combinations into ovarian cancer clinical trials,” says Matulonis.
She notes that treatment advances in ovarian cancer have reached a plateau. “Newer agents that target ovarian cancer genetic abnormalities have shown some efficacy as single agents, but cancer cells eventually figure out ways to grow despite the drug,” says Matulonis. Because of that, Matulonis and her team will explore a number of strategies that combine drugs that simultaneously target several abnormal biologic pathways in ovarian cancer cells. In one project, researchers will test the effectiveness of a PARP inhibitor and another targeted therapy in blocking the abnormal PI3-kinase signaling pathway in ovarian tumors.
A second project will combine two drugs – a heat shock protein (HSP) inhibitor and a PARP inhibitor – aimed at preventing damaged ovarian cancer cells from repairing themselves. The third project will use a technique called BH3 profiling, which measures how close cancer cells are to destroying themselves, to evaluate targeted drug combinations.
Other investigators funded by the grant are Gerburg Wulf, MD, PhD, of Beth Israel-Deaconess Medical Center; and Dana-Farber researchers Panagiotis Konstantinopoulos, MD, PhD; Anthony Letai, MD, PhD; Joyce Liu, MD, MPH, and William Barry, PhD.