DFCI Logo
DFCI Logo

Center for BRCA and Related Genes Clinical Trials and Research

    In this section
    df_bcc_pos_rgb.png

    New Patient Appointments

    877-442-3324
    REQUEST AN APPOINTMENT
    brca-and-related-genes-leadership-653x447.jpg

    Basic (Pre-Clinical) Research for BRCA-Mutated and BRCA-Related Cancers

    Dana-Farber has an unparalleled legacy in the basic research arena of BRCA genes, starting with the work of David Livingston, MD, in the early characterization of BRCA1 gene expression in breast and ovarian tumor cells and the subsequent discovery of other BRCA-related genes (PALB2, BRIP1, and BARD1). Alan D'Andrea, MD, discovered the connection of the BRCA genes with the genetic disease, Fanconi anemia, and also the link of BRCA-related genes with polymerases that can be therapeutically targeted.

    Dana-Farber has continued this outstanding track record of discoveries in the basic biology of BRCA1/2 and other genes critical for DNA repair to complement our groundbreaking translational and clinical research. We also have a track record of prestigious funding awards, such as from Stand Up to Cancer and National Cancer Institute (NCI) Specialized Programs of Research Excellence (SPORE) grants in breast, ovarian, and gastrointestinal cancers. Research performed in the The Mellen and Eisenson Family Center for BRCA and Related Genes encompasses chemoprevention, development of novel therapies, and innovative early detection strategies across related diseases.

    Areas of Basic Research Interest

    There are three main thematic/focus research areas: therapy, risk reduction (prevention), and early detection. In addition to the BRCA center's clinical research and clinical trials, our center is active in all these areas with multiple basic and translational research projects.

    Therapy

    In addition to developing novel therapies for patients with BRCA-related cancers through clinical trials, our center focuses on development of novel biomarkers of response; on development of disease models to test novel therapies preclinically; and on elucidating mechanisms of resistance to these therapies. We are also exploring novel strategies to enhance the activity of immunotherapy in BRCA-mutated tumors by trying to transform immunologically "cold" tumors (tumors that have not been recognized or have not provoked a strong response by the immune system) into "hot" tumors (tumors that have provoked a strong immune response), which are more likely to respond to immunotherapy.

    Novel models: A very important area of interest has been the development of novel models of BRCA-related cancers. Examples of such models include:

    These models are invaluable platforms for preclinical development of novel therapeutic agents, including novel immunotherapy approaches that can then be tested in clinical trials. These platforms also provide the opportunity to study the biology of BRCA-related cancers.

    Overcoming resistance: Another focus is on understanding and overcoming resistance to chemotherapy and other targeted therapies. Current studies focus on high-throughput approaches, such as genome-scale CRISPR-Cas9 knockout screens in BRCA-related tumors to gain insight on factors/pathways regulating sensitivity and resistance to specific therapies, as well as small molecule screens to identify agents that can restore therapeutic sensitivity in tumors that are resistant to specific therapies.

    Risk Reduction (Prevention)

    Another key priority of our center, in collaboration with Dana-Farber's Center for Cancer Genetics and Prevention, is to offer novel cancer risk reduction strategies to patients who are carriers of BRCA1/2 mutations and related genes. Our center focuses on developing and implementing novel systems to expand genetic testing to all who may benefit from the information, based on the most recent guidelines.

    Additionally, our center works with Dana-Farber investigators to understand the process of carcinogenesis (i.e., how BRCA-mutated and related cancers evolve) and to identify the earliest events using cellular, molecular, and immunologic assays on precursor lesions. Understanding the earliest events in BRCA tumor development may provide novel targets for cancer prevention. Ongoing basic research work focuses on dissecting the DNA repair functions of the BRCA1/2 and other BRCA-related genes and elucidating BRCA regulatory and BRCA-independent DNA repair mechanisms that contribute to the development of breast, ovarian, and other BRCA-related cancers (such as prostate and pancreatic cancers).

    Early Detection

    A major priority of our center is early detection, with a focus on ovarian and pancreatic cancers, for which there are currently no reliable and effective screening tests. Dipanjan Chowdhury, PhD, 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. This test has very promising accuracy in detecting ovarian cancer and discriminating from benign ovarian lesions and healthy controls. 

    Center for BRCA and Related Genes Scientific Symposium

    The Center for BRCA and Related Genes hosted the 2nd annual scientific symposium featuring Harvard Medical School faculty and prominent experts and leaders in their field on November 15, 2023. This symposium was for clinicians, researchers, patients, and donors who were interested in learning more about BRCA1/2 and related genes and exploring the latest research in a variety of cancer types affected by mutations in the BRCA pathway.

    Check back for information about the 2024 Center for BRCA and Related Genes Scientific Symposium.

    VIEW HIGHLIGHTS FROM THE 2023 SYMPOSIUM

    Clinical Trials for BRCA-Mutated and BRCA-Related Cancers

    An important priority of our center is to provide novel therapies for patients with BRCA-mutated and BRCA-related cancers through clinical trial participation. The center offers novel resources and therapies in the form of clinical trials and studies — spanning early and late phases of therapy, risk reduction (prevention), decision-making, and early detection, as well as quality of life and survivorship.

    For patients and families with Lynch syndrome and Li-Fraumeni-related cancers, more information on trials and therapies is available from the Lynch Syndrome Center and the Li-Fraumeni Syndrome and TP53 Center at Dana-Farber.

    Patients can enter trials that are conducted:

    Therapeutic Trials

    For treatment, Dana-Farber boasts one of the largest portfolios of clinical trials nationally addressing novel therapeutics for patients with inherited and acquired mutations in BRCA1/2 and related DNA-repair genes in ovarian, breast, pancreatic, prostate, and other cancers.

    A Special Focus on Resistance

    Dana-Farber has played a critical role in the development and eventual FDA approval of PARP inhibitors for ovarian, breast, pancreatic, and prostate cancers; we are also evaluating strategies for patients with tumors that are intrinsically resistant or that have developed resistance to PARP inhibitors. Our center has a special focus on patients who are heavily pretreated and whose cancers have developed resistance to chemotherapy, targeted agents, and DNA repair inhibitors such as PARP inhibitors.

    We are examining agents such as ATR inhibitors, WEE1 inhibitors, and other cell cycle checkpoint inhibitors, as well as targeted agents including PI3K inhibitors, CDK inhibitors, MAPK pathway inhibitors, and HSP90 inhibitors, alone or in combination with immunotherapy such as PD-1/PD-L1 inhibitors. We are also using PARP inhibitors to further augment the activity of antibody-drug conjugates and immunotherapy. Many of our trials and studies are investigator-initiated, based on preclinical data developed at Dana-Farber using various disease models such as patient-derived xenograft models, organoid models, and genetically engineered mouse model platforms.

    Eligible participants for these clinical trials include not only patients with BRCA-mutated cancers but also patients with inherited and acquired somatic (tumor-only) mutations in other BRCA-related genes such as PALB2, RAD51C, and others.

    Featured Therapeutic Clinical Trials

    Trial 20-371: Phase 2 study of niraparib with dostarlimab therapy as neoadjuvant treatment for patients with BRCA-mutated breast cancer
    Principal investigator: Erica L. Mayer, MD, MPH

    Trial 21-311: MYTHIC: Phase 1 study of the safety, pharmacokinetics, pharmacodynamics and preliminary clinical activity of RP-6306 alone or in combination with RP-3500 in patients with advanced solid tumors
    Principal investigator: Elizabeth K. Lee, MD

    Trial 21-667: Phase 1 study of RO7623066 alone and in combination in patients with advanced solid tumors
    Principal investigator: Elizabeth K. Lee, MD

    Trial 23-211: Phase 1/2, open-label study to evaluate the safety, tolerability, pharmacokinetics, and efficacy of INX-315 in patients with advanced cancer
    Principal investigator: Antonio Giordano, MD, PhD

    Trial 23-643: Phase 1/2, multi-center, open-label study to evaluate the safety, tolerability, and preliminary antitumor activity of TNG348 single agent and in combination with a PARP inhibitor in patients with BRCA1/2 mutant or other HRD+ advanced or metastatic solid tumors
    Principal investigator: Alok K. Tewari, MD, PhD

    Trial 23-600: Study of PARG inhibitor IDE161 in participants with advanced solid tumors
    Principal investigator: Filipa Lynce, MD

    Trial 23-235: Phase 1 study of the polymerase theta (POLθ) inhibitor novobiocin in BRCA-mutant and other DNA damage repair-deficient solid tumors
    Principal investigator: Geoffrey Shapiro, MD, PhD

    Trial 20-320: CAPRI: Combination ATR and PARP Inhibitor trial with AZD6738 and olaparib in recurrent ovarian cancer
    Principal investigator: Joyce F. Liu, MD, MPH

    Trial 20-271: Phase 1/1b dose escalation study of pegylated liposomal doxorubicin with peposertib (M3814) in platinum-resistant or ineligible ovarian and related cancers with planned expansions in high grade serous and low grade serous ovarian cancer
    Principal investigator: Panagiotis (Panos) A. Konstantinopoulos, MD, PhD

    Trial 19-059: EFFORT: EFFicacy Of ceralasertib (AZD6738) and adavosertib (AZD1775) in PARP ResisTance; A randomized 3-arm non-comparative phase 2 study of adavosertib alone, adavosertib plus olaparib, and ceralasertib plus olaparib in women with ovarian cancer who have progressed during PARP inhibition
    Principal investigator: Joyce F. Liu, MD, MPH

    Trial 21-580: Phase 1b study of ZN-c3 in combination with chemotherapy or bevacizumab in patients with platinum-resistant ovarian, peritoneal, or fallopian tube cancer
    Principal investigator: Joyce F. Liu, MD, MPH

    Trial 23-205: ARTIST: Phase 2, open-label, multi-center, basket study of the ATR kinase inhibitor ART0380 administered orally as monotherapy to patients with biologically selected advanced or metastatic solid tumors
    Principal investigator: Panagiotis (Panos) A. Konstantinopoulos, MD, PhD

    Trial 23-221: Phase 1b/2 basket study of ACR-368 as monotherapy and in combination with gemcitabine in adult subjects with platinum-resistant ovarian carcinoma, endometrial adenocarcinoma, and urothelial carcinoma based on Acrivon OncoSignature® status
    Principal investigator: Panagiotis (Panos) A. Konstantinopoulos, MD, PhD

    Trial 23-613: Phase 2 open-label, multicenter study to evaluate efficacy and safety of ZN-c3 in subjects with high-grade serous ovarian, fallopian tube, or primary peritoneal cancer
    Principal investigator: Joyce F. Liu, MD, MPH

    Risk Reduction (Prevention) and Decision-Making Trials

    The Center for Cancer Genetics and Prevention is home to several studies and clinical trials to evaluate the potential of different strategies to delay or prevent the development of cancer in BRCA mutation carriers and to improve education for this population. Various novel approaches are being explored including peer support, genetic counseling and education, and targeted agents such as the RANKL inhibitor denosumab.

    Featured Risk-Reduction and Decision-Making Studies Clinical Trials

    Trial 21-297: Parent Communication Study IV: Improving genetic counseling for BRCA+ mothers
    Principal investigator: Huma Q. Rana, MD, MPH

    Trial 22-110: CASCADE: CAncer Susceptibility Counseling And Decisions
    Principal investigator: Huma Q. Rana, MD, MPH

    Trial 22-212: BRCA-P: Randomized, double-blind, placebo-controlled, multi-center, international phase 3 study to determine the preventive effect of denosumab on breast cancer in women carrying a BRCA1 germline mutation
    Principal investigator: Judy E. Garber, MD, MPH

    Early Detection Research

    The early detection MiDe Study (MicroRNA for early Detection) of ovarian cancer has been launched to evaluate the potential of circulating serum microRNAs (miRNAs) as a screening test for ovarian cancer in healthy BRCA-mutation carriers. Not all BRCA carriers may develop cancer, and more importantly, we don't know when the malignant tumor will develop. Dipanjan Chowdhury, PhD, and Kevin Elias, MD, have developed a non-invasive diagnostic test to monitor BRCA carriers and assess their risk of developing ovarian cancer. In collaboration with Judy Garber, MD, MPH, this study has been initiated to formally develop a screening test for early detection of ovarian cancer in families with mutations in BRCA and BRCA-related genes. Analogous efforts for the early detection of cancer are ongoing through the Li-Fraumeni Syndrome and TP53 Center at Dana-Farber.

    What to Expect

    At Dana-Farber, your treatment team is based in one of our specialized disease centers for different cancer types. You may be referred to the Center for BRCA and Related Genes to discuss the possibility of participating in a clinical trial, but you will remain under the care of your original team.

    When you come to the center for a clinical trial, we will provide you with specific information about what your participation will entail. We will make sure you, your family, and your treatment team understand all aspects of your involvement in the trial.

    Our center's staff is devoted to pursuing excellence in the safe conduct of clinical trials for cancer, with compassion and respect for everyone involved.