2013 Mentored Investigator Grant Recipient — Diana Hargreaves, PhD
Project Summary
Ovarian cancer is the most lethal of the gynecological malignancies. Ovarian tumors can be particularly difficult to treat as they are often not responsive to the chemotherapeutics that are currently in use for the treatment of ovarian cancer. Recently, it was found that some types of ovarian cancer have mutations in the ARID1A gene and lack ARID1A protein expression. These mutations were found in tumors, but not in normal tissue from the same patient, suggesting a causal link between loss of ARID1A protein and tumor initiation or growth. Paradoxically, loss of ARID1A causes growth arrest and cell death, not the uncontrolled cell division that occurs in cancer. Thus, there must be mutations in other proteins that cooperate with mutations in ARID1A to drive tumor formation. Recent data suggests that mutations in ARID1A are most often paired with mutations in an enzyme called PI 3-Kinase for which drugs have been developed. This proposal aims to understand how cells respond to mutations in these two different proteins to become cancerous. With this mechanistic understanding, we hope to determine how this class of ovarian tumors responds to PI 3-Kinase inhibitors with the aim of providing better, more personalized chemotherapeutic treatment.
This grant was made possible through the generous support of the University of California Office of the President’s Tobacco-Related Disease Research Program.