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Adrienne Waks, MD
Fellow in Medical Oncology
Dana-Farber Cancer Institute
Conquer Cancer Foundation of ASCO
- Seeking to identify strategies to reduce drug resistance in patients with BRCA1/BRCA2 metastatic breast cancer.
- Studies in patient tumor samples are conducted to identify cellular changes during treatment that may lead to drug resistance.
- These studies will provide new clues to resistance to DNA damaging therapies and potentially uncover markers to predict which patients are most likely to benefit.
The recent approval of the PARP inhibitor, olaparib (Lynparza) offers a less toxic treatment alternative for patients with advanced breast cancers with BRCA 1/BRCA2 gene mutations. Not all patients benefit equally and resistance to this and other similar drugs remains a clinical challenge. Dr. Waks is pursuing studies to understand how resistance to these therapies occurs and to identify markers that can predict which patients will most likely benefit.
Full Research Summary
Breast tumors that cannot adequately repair cellular DNA damage, such as those caused by mutations in the BRCA1 and BRCA2 genes, may be particularly susceptible to cancer therapies that cause DNA damage. These include platinum-based chemotherapies and a newer class of drugs called PARP inhibitors, such as olaparib (Lynparza®). Olaparib was recently FDA approved for the treatment of metastatic breast cancer associated with a BRCA1 or BRCA2 mutation. Unfortunately, not all patients with BRCA1/2 breast cancers benefit from this targeted approach, and for some that do, the treatment may stop working allowing the cancer to come back or spread.
The goal of Dr. Waks’ Conquer Cancer Foundation project supported by BCRF is to understand how resistance to PARP inhibitors or platinum chemotherapy develops. To accomplish this, she will analyze the DNA and RNA of tumor biopsies from patients with metastatic breast cancer and BRCA1/2 gene mutations both before and after they undergo treatment with a PARP inhibitor or platinum chemotherapy. She will look for changes in the tumor DNA and RNA between the time the patient was responding to therapy and the time she stopped responding to better understand the changes that lead to the development of drug resistance. In addition, she will conduct experiments in tissue biopsies to determine how alterations in BRCA1/2 proteins affect the development of drug resistance to DNA damaging agents.
These experiments will help identify breast cancer patients who are most likely to benefit from PARP inhibitors or platinum chemotherapy and may help to guide the development of new treatment strategies for patients who become resistant to these treatments
Dr. Waks conducted her undergraduate studies at Princeton University and then obtained her MD degree at Harvard Medical School. She completed residency training in internal medicine at Brigham and Women's Hospital in Boston, MA, where she was selected to serve for an additional year as a Chief Resident in internal medicine. She completed clinical and research fellowship training in medical oncology at Dana-Farber/Partners Cancer Care, then joined the medical oncology staff of the Breast Oncology Center at Dana-Farber Cancer Institute.
BCRF Investigator Since