Grants Program

The Basser Center for BRCA has the unique opportunity to catalyze research to change the paradigm of discovery, innovation, and care for issues related to BRCA1 and BRCA2 mutations. Germline mutations in BRCA1 and BRCA2 significantly increase the risk of breast and ovarian cancer and also are associated with prostate cancer and pancreatic cancer. Towards this end, the Basser Center is seeking applications that propose innovative approaches to the study of BRCA-related cancers.

The application period for 2025 is now closed.

The Basser Center for BRCA at Penn Medicine’s Abramson Cancer Center announces the Basser External Research Grant Program, which focuses on projects that have the potential to advance the care of individuals living with BRCA1 and BRCA2 mutations. Research grant applications in basic science, prevention, disease interception, and early detection and relevant to the study of BRCA1/2 will be considered. 

The application period for 2025 is now closed.

Angela Bradbury, MD
The eREACH study (A Randomized Study of an eHealth Delivery Alternative for Cancer Genetic Testing for Hereditary Predisposition in Metastatic Breast, Ovarian, Pancreatic and Prostate Cancer Patients) will evaluate the effectiveness of a theoretically and stake-holder informed eHealth delivery alternative to traditional genetic counseling in patients with advanced breast and ovarian cancer. Dr. Bradbury expects this alternative delivery model for genetic testing has the potential to provide equal or improved patient outcomes, while reducing patient and genetic provider time and increasing uptake of testing in patients who can benefit from genetic testing. The study is anticipated to open in Spring 2019 and will recruit over 400 patients with advanced breast and ovary cancer.

Ronny Drapkin, MD, PhD
Animal models are the backbone of cancer research and can illuminate facets of tumor development, progression, and response to therapy. Robust models for ovarian cancer have been difficulty to develop in part because it is a very heterogeneous disease. The appreciation that the tumor microenvironment imposes constraints on tumor cell biology emphasize the need to develop models in an immunocompetent setting. The goal of this project, A Fallopian Tube Derived Syngeneic Mouse Model of BRCA-Related Ovarian Cancer, is to create such a model. To achieve this goal, the team isolated cells from the fallopian tubes (the primary site of origin for most BRCA-associated ovarian cancer) of immunocompetent mice and used genome-editing to create defects in key oncogenes and tumor suppressor genes that would allow for a tumor to form when the cells are implanted back into the abdominal cavity of the mouse. This enables the team to explore the specific contribution of BRCA mutations on disease development, progression, and how the microenvironment reacts to these tumors and whether the genetic makeup of the tumors (e.g., BRCA vs non-BRCA) influences those interactions. 

Roger Greenberg, MD, PhD
The goal of this study, BRCA Function in the DNA Damage Response, is to identify and target mechanisms of resistance to PARP inhibitors (PARPi) and Platinum based chemotherapies in BRCA1 and BRCA2 mutant cancers. This work has led to the initiation of clinical trials using approaches to identify patients that are more likely to respond to PARPi therapy. Dr. Greenberg’s lab has made substantial progress stemming from their discoveries as part of their earlier team science grant. The team defined alternative pathways to BRCA-Rad51 recombination that are required for survival in BRCA mutant cells. They have also identified the entire network of these alternative DNA repair mechanisms, providing a rich source of factors to investigate in BRCA mutant cells that have become resistant to PARPi. Another aspect of the research comes from discovery of a new gene that is required for survival of BRCA mutant cells and dramatically increases their sensitivity to PARPi. This work is a promising avenue to begin drug discovery efforts.

Katherine L. Nathanson, MD 
The team's projects, including Phenotypes of BRCA1/2 Mutation Carriers From Population Based Databases to Tumor Development, focus on understanding the phenotypes associated with BRCA1/2 mutations, in particular related to genotype-phenotype correlations. This on-going project analyzes primary BRCA1/2 mutation-associated breast cancers to evaluate whether molecular and pathological features vary between breast tumors associated with different mutational types (missense, large genomic rearrangements vs. frameshift/truncating) and locations (exon 11 vs. non-exon 11). They also are interested in examining the Penn Medicine Biobank to determine whether mutation type and location can be associated with clinical features. They continue to evaluate whether allele-specific loss of heterozygosity is associated with outcome and are using a large well characterized sample set to do so. They are evaluating matched primary and recurrent BRCA1/2 mutated breast and ovarian cancer to identify recurrent specific features that can potentially be therapeutically targeted. We have identified several potential features that may be of interest, including some that are associated with significant differences in survival, but the results are preliminary and need further validation.

Robert H. Vonderheide, MD, DPhil
The Basser funded study, TERT DNA Vaccination and Immune Modulation in a BRCA Mutant Mouse Model of Pancreatic Cancer, which is co-led by David B. Weiner, PhD (The Wistar Institute), is exploring the use of a TERT DNA vaccination in combination with immune modulation to prevent tumor development in a BRCA2 deficient pancreatic cancer model. This is a continuation of research that began during a Basser Team Science award, where the Weiner and Vonderheide laboratories collaborated to i) demonstrate synergy between TERT DNA immunization and immune checkpoint blockade in other tumor models, and to ii) develop a transgenic pancreatic ductal adenocarcinoma model lacking BRCA2 expression, termed the KPC-B model. In continuation of this work, this team will examine the impact of TERT DNA immunization either alone,in combination with immune checkpoint inhibitors targeting CTLA4 or PD1, or in combination with CD40 mAb or CD40L plasmid adjuvant using the KPC-B model. Their goal is to utilize these pre-clinical results to design a clinical trial for immunization of high risk BRCA1/2 mutation carriers.