Of the tens of thousands of genes in the DNA of our cells, one group of genes is tasked with the critically important job of ensuring that every cell reproduces itself exactly when it divides to make new cells. Perhaps the best known of these “DNA repair genes” are the BRCA genes, which if inherited with a significant alteration, confer a markedly increased risk of certain cancers over a lifetime. Moreover, it is now clear that many cancers can acquire mutations in the BRCA and other related DNA repair genes only in their tumor cells, even though the patient was not born with the genetic mutation. As the importance of these genes has become increasingly evident in the risk, growth, and treatment of cancer, Dana-Farber Cancer Institute is launching a new center of excellence – the Center for BRCA and Related Genes – dedicated to the care for, prevention of and research into BRCA-related cancers.
Patients with inherited BRCA mutations, as well as those with acquired BRCA mutations only in their tumors, are increasingly likely to benefit from new classes of drugs such as PARP inhibitors and other cell cycle checkpoint inhibitors, as well as targeted agents alone or in combination with immunotherapies. An important priority of the new Center for BRCA and Related Genes will be to provide access to these novel therapies for patients with BRCA-mutated and BRCA-related cancers through clinical trials, with a particular focus on overcoming developed resistance to chemotherapy, targeted agents, and DNA repair inhibitors.
“Recent research at Dana-Farber and other leading cancer centers has identified genetic defects in BRCA-related tumors that make them vulnerable to new effective treatments,” said Panos Konstantinopoulos, MD, PhD, Director of Translational Research, Gynecologic Oncology at Dana-Farber and Director of the new Center. “The rapid accumulation of insights into DNA repair genes in an expanding array of cancers, and the development of new and emerging targeted therapies exploiting defects in DNA repair provide the perfect opportunity for a dedicated comprehensive Center to help accelerate progress.”
Patients visiting the new Center for BRCA and Related Genes will be evaluated by an appropriate designated expert Dana-Farber physician, with a genetics evaluation as needed. Teams of specialists at the Center will work closely together to offer patients the latest therapies and clinical services, including access to innovative clinical trials.
“Dana-Farber has been a leader in basic and clinical research into BRCA and related genes, and provides expert care for individuals and families with inherited errors in them,” said Judy Garber, MD, MPH, Chief of Dana-Farber’s Cancer Genetics and Prevention division and a co-director of the new Center. “The new Center will also feature our trials of novel cancer risk reduction strategies for patients who are carriers of BRCA1/2 mutations and related genes, and our work to further expand genetic testing to all who may benefit from this critical information.”
In addition to the treatment and prevention of BRCA-related cancers, another major priority of the Center is early detection of these diseases, with a focus on ovarian and pancreatic cancers, for which there are currently no reliable and effective screening tests.
Dipanjan Chowdhury, PhD, Chief of the Division of Radiation and Genome Stability at Dana-Farber Cancer Institute, who will co-direct the Center, and Kevin Elias, MD, have discovered a specific set of 14 circulating microRNAs (miRNAs) in the serum of ovarian cancer patients that may be used for early detection of the disease.
The researchers have recently initiated a study to formally develop a screening test for early detection of ovarian cancer in families with mutations in BRCA and BRCA-related genes.
"Cancer detected early is more curable, so the development of accurate and sensitive tests for the early cancer detection is an enormous priority for high risk families and for all woman at risk for ovarian cancer,” said Dr. Chowdhury. “The MiDe Study (MicroRNA for early Detection) of ovarian cancer we recently launched and will continue through the Center, may allow us to develop such a test, and eventually monitor high-risk family members with an accurate blood test for ovarian cancer."
Finally, the Center will work with leading investigators who study BRCA and related genes both at Dana-Farber, nationally and internationally, to accelerate progress in the field.
Aa dedicated advisory committee chaired by Geoffrey Shapiro, MD, PhD Senior Vice President for Drug Development at Dana-Farber, will help oversee the activities of the center and its institutional collaborations.