The University of Pennsylvania's Basser Research Center for BRCA has announced $6.9 million to research teams both at Penn and at five other institutions across the United States, aimed at advancing the care of patients living with BRCA1 and BRCA2 mutations through multi-disciplinary collaboration. Penn Medicine's Abramson Cancer Center, home to the Basser Center, will serve as steward of the grants.
The new funding includes the first recipients of the new Basser External Research Grant Program, a unique funding mechanism for high-impact translational cancer research projects with the potential to advance rapidly into clinical practice.
"The projects funded this year are at the forefront of BRCA-related cancer research, and will help bring targeted therapies to a new level," said Susan Domchek, MD, executive director of the Basser Research Center for BRCA and the Basser Professor of Oncology at the Abramson Cancer Center. "BRCA research has come so far since the initial discovery twenty years ago, and working in collaboration with colleagues across the nation, we are making strides every day toward providing better care for these high-risk patients."
Among the five external recipients is a multi-institutional team led by Junjie Chen, PhD, chair of the department of Experimental Radiation Oncology at the University of Texas MD Anderson Cancer Center in Houston. The group is the recipient of the first Basser Team Science Award, which will fund a project focusing on developing new forms of chemotherapy for BRCA1/2-related cancers, and overcoming resistance to these medications.
Other recipients of funding through the External Grants Program include research teams at Johns Hopkins University, Fox Chase Cancer Center, and Drexel University College of Medicine, all of whom will work to enhance the effectiveness of various therapies which have potential for alleviating BRCA1/2-related cancers. For example, the project led by researchers at Drexel University College of Medicine will work to analyze the effect of specific genetic inhibitors in BRCA1/2 cells alone and in combination with therapeutic drugs, and to study the mechanisms of homologous recombination - a key pathway to repairing DNA damage - in human cells. In contrast, the project led by the team at Fox Chase Cancer Center, will aim to identify and characterize additional BRCA1 mutations that are capable of contributing to DNA repair and drug resistance. Researchers at Columbia University, who will design and conduct a community outreach effort aimed at minority women to determine eligibility for genetic counseling, also received funding.
The External Grants Program was made possible by a $5 million donation made earlier this year by University of Pennsylvania alumni Mindy and Jon Gray. Their latest gift brings their total giving to Penn to $30 million, following a $25 million gift which established the Basser Center in 2012. The Center was created in memory of Mindy Gray's sister Faith Basser, who died of BRCA-related ovarian cancer at age 44.
"We are enormously grateful to the Grays for extending their generosity to support these research programs," said Domchek. "Their gift allows us to work more closely in collaboration with colleagues at academic institutions around the world. In a time when medicine is making such great strides but federal funding for biomedical research is waning, it's vital that we find new channels to continue supporting progress across the field of BRCA research."
Funding for Penn investigators includes four new grants:
Breakthrough Science Team Awards
Vaccination to Prevent BRCA1/2-Related Cancers: This project will study the development of a novel vaccine to prevent BRCA1/2-related cancers in healthy individuals who carry BRCA1/2 mutations. As a first step toward this overall goal, the study will work to determine the clinical and immunological impact of vaccinating high-risk patients in remission after adjuvant therapy using TERT DNA with or without IL-12 DNA. Investigators: Robert Vonderheide, MD, DPhil, David Weiner, PhD, Daniel Powell,PhD, Andrea Facciabene, MD, PhD, Katherine Nathanson, MD, E. John Wherry, PhD, and Ben Stanger, MD.
Molecular Determinants of Chemo-Responsiveness of BRCA Mutant Cancers: Funded to study the molecular basis of cell intrinsic and extrinsic mechanisms that dictate chemo-responsiveness of BRCA mutant cancers, this project will work to identify novel strategies that overcome common mechanisms of resistance. Investigators: Roger Greenberg, MD, PhD, Lin Zhang, MD, Andy Minn, MD, and Warren Pear, MD.
Targeting the ATR/CHK1 Pathway in Treatment: A project focused on determining if ovarian and pancreatic BRCA2-deficient cancers can be treated by targeting the ATR/CHK1 pathway as a primary line of therapy, or be used secondarily following the development of PARPi resistance. Investigators: Eric Brown, PhD, Fiona Simpkins, MD, Rugang Zhang, PhD, and Mark Morgan, MD.
Outreach and Implementation Science Award
Optimizing Precision Risk Assessment and Access to Genetic Services for BRCA1/2 Mutation Carriers: This project will improve risk estimation and enhance and improve access to expert genetic providers in geographically and sociodemographically diverse populations with limited access to genetic services. Investigators: Timothy Rebbeck, PhD, Angela Bradbury, MD, Katherine Nathanson, MD, and Jinbo Chen, PhD.