University of California
San Francisco Center for BRCA Research

There has been considerable research into how BRCA mutations heighten the risk of cancer. Promising avenues for new therapies hold out the prospect of a cure for BRCA-related cancer, although significant effort is still required to achieve this goal. Prevention will be the ultimate solution for many affected family members, but this will not be possible in the short- to medium term. In the meantime, we must urgently address who is most at risk and devise treatments with the goal of curing cancers that arise in BRCA carriers. In order to receive BRCA-directed care, BRCA carriers with cancer and their family members will require a comprehensive approach to diagnosis, screening, and treatment by experts in this disease. AT UCSF, our overall aim is to translate cutting-edge basic research into clinical benefit by building a highly integrated and coordinated research program. We will also ensure we leverage knowledge of BRCA-mutation-related cancers to improve therapy for patients both with BRCA-mutation-related cancers and those that have similar molecular properties. Alan Ashworth and colleagues have termed this phenomenon ‘BRCAness.’

The Center for BRCA Research is addressing key questions: What are the optimal combinations of PARP inhibitors and other therapeutic agents? What are the determinants of BRCAness in diverse diseases such as prostate cancer, pancreatic cancer and ovarian cancer? What are the effects of heterogeneity in BRCA-related cancers? Can we develop molecular markers of response and resistance to PARP inhibitors? Our laboratory seeks to identify, develop, and optimize new therapeutic approaches to the treatment of BRCA cancer. We use synthetic lethal concepts developed by UCSF scientists to optimize the use of inhibitors that can increase the efficacy of anticancer agents by targeting DNA-repair enzymes in the Poly(ADP-ribose) polymerase (PARP) family; develop combination approaches to overcome resistance; and develop novel approaches. We will also apply the knowledge we gain to those tumors with BRCAness— perhaps up to 25% of human cancers— and develop biomarkers to identify such tumors.