The Future of BRCA

The V Foundation has joined forces with the BRCA Foundation to put an end to BRCA related cancers!

BRCA 1 and 2 genes are tumor suppressor genes, and we all have them. When working properly, they control the way cells grow in certain tissues in the body. However, when mutated, they can increase the possibility for certain types of cancer to arise. While BRCA gene mutations were first noted to cause higher rates of breast and ovarian cancer and remain prominently linked to those cancers, research has shown they can trigger a variety of cancers throughout the body, in men and women. Learn more about BRCA from the Basser Center, the first comprehensive center for research, treatment and prevention of BRCA-related cancers.

The BRCA Foundation, spearheaded by Evan and Cindy Goldberg, has committed to join forces with the V Foundation for Cancer Research to fund researchers with new and innovative ideas on how to prevent, treat and cure BRCA related cancers. Goldberg, a V Foundation Board Member since 2014, is the Chairman, President and Director of the BRCA Foundation. The mission of the BRCA Foundation is to accelerate research and foster collaboration in order to prevent and cure BRCA cancers.

BRCA mutations can affect both men and women and be passed down by either parent. They can increase lifetime risk for cancers including breast, ovarian, pancreatic, prostate and melanoma. In fact, BRCA mutations give an increased risk of lifetime cancer of up to 75% for breast, up to 50% for ovarian and up to 25% for prostate.

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BRCA-Related Grants

Karlene Cimprich, Ph.D.
Stanford Cancer Institute
Stanford, CA
BRCA 1/2 Mutation Associated R-Loops: Roles in Genomic Instability and Biomarker Development
Funded by 2017 BRCA Fund-A-Need

To improve cancer detection and treatment for women with BRCA1 or BRCA 2 mutations, Cimprich and her team examine how certain mutations may cause DNA to break. Having discovered that tangled clumps of RNA and DNA, known as R-loops, can break a DNA strand, the team is exploring how R-loops break and whether they could serve as a sensitive marker for early cancer detection.

Judy Garber, M.D., MPH
Co-PI: Myles Brown, M.D.
Dana-Farber Cancer Institute
Boston, MA
Development of Effective Hormonal Chemoprevention for BRCA 2 Carriers
Funded by 2017 BRCA Fund-A-Need

When women with a BRCA2 mutation have their ovaries removed – typically as a preventative measure due to their high risk of ovarian cancer – they often develop menopause symptoms. However, conventional hormone replacement menopause therapies may increase the risk of breast cancer. This exciting clinical trial is evaluating whether a new combination therapy could offer these women relief from menopause symptoms while helping to protect them against breast cancer.

Roger Greenberg, M.D., Ph.D.
University of Pennsylvania
Philadelphia, PA
Understanding and Exploiting the Heterogeneity of Cell Intrinsic and Extrinsic Responses to DNA Damage in BRCA mutant Cancers
Funded by 2017 BRCA Fund-A-Need

Cancers that are related to BRCA mutations often become resistant to available medications. To overcome this problem, Greenberg’s team is taking a new approach – taking advantage of the body’s natural inflammatory and immune responses to target drug-resistant cancer cells – in hopes of developing a better cure for BRCA related cancers.

Tony Huang, Ph.D.
Co-PIs: Eli Rothenberg, Ph.D. (NYU), Douglas Levine, M.D. (NYU), and Ryan Jensen, Ph.D. (Yale)
New York University School of Medicine
New York, NY
Elucidating the Replication Fork Protection Problem Caused by PARP inhibitors in BRCA2-mutated Ovarian Cancers
Funded by 2017 BRCA Fund-A-Need

Drugs known as PARP inhibitors have made a huge difference for many patients with ovarian cancer who have BRCA2 mutations, but they don’t work for everyone. To inform clinical decision making and identify potential new treatments, this research project aims to uncover how PARP inhibitors interact with ovarian tumors and why some BRCA related cancers become resistant to them.

Fiona Simpkins, M.D.
Co-PIs: Eric Brown, Ph.D. and Payal Shah, M.D.
University of Pennsylvania
Philadelphia, PA
Novel PARP and ATR inhibitor combination therapies for BRCA-mutant ovarian cancer
Funded by 2017 BRCA Fund-A-Need

In a new clinical trial, Simpkins and her team are testing a combination therapy designed to improve the effectiveness of PARP inhibitors in women with BRCA related ovarian cancer. With V Foundation funding, the team is working to identify ways to predict which patients are likely to benefit most from the new therapy and to further refine the drug combination to create the most effective and well-tolerated treatment possible.

Alan Ashworth, Ph.D.
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California
Towards Making PARP Inhibitors a curative treatment for BRCA-related cancers
Funded in partnership with the Goldberg Family Foundation and in collaboration with the Gray Foundation

Using functional genomic approaches, Ashworth and team are investigating mechanisms of resistance and identifying novel genetic vulnerabilities that can be exploited by PARPi treatment. They are also investigating the immune response to BRCA-mutant tumors and exploring ways to improve the ability of immune cells to recognize and kill these tumors. The ultimate goal of these studies is to improve outcomes for patients with BRCA-mutant tumors and to identify new groups of patients that can benefit from PARPi.

James Ford, M.D.
Stanford University School of Medicine
Stanford, California
Stanford Genetic Studies of BRCA1/BRCA2 Associated Tumors & Blood Samples
Funded in partnership with the Goldberg Family Foundation

Dr. Ford and team are screening for cancer in high-risk individuals using Liquid Biopsies. As part of their collaboration with V Foundation funded investigator Karlene Cimprich, they have begun to look for “R-loops”, abnormal DNA-RNA hybrids formed in response to DNA damage in BRCA mutant cells, in patient plasma samples. Early studies suggest that they can detect these potential biomarkers in plasma.

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The Future of BRCA