Alan D'Andrea, MD

2012-2013 BCRF Project:
A subset of breast cancers has an underlying defect in DNA repair. This defect results, in some cases, from inherited mutations in the breast cancer susceptibility genes, BRCA1 or BRCA2. Because of this DNA repair defect, these tumors are hypersensitive to a new drug class, referred to as PARP inhibitors. Dr. D'Andrea's laboratory has recently demonstrated that another drug (bortezomib) can block DNA repair. Through BCRF support, Dr. D'Andrea's laboratory is evaluating the combination of bortezomib plus PARP inhibitor in preclinical breast tumor studies. His laboratory has continued to examine the combination of two drugs in the treatment of triple negative breast cancer. These researchers have shown that this combination is more successful at killing a human breast tumor cell line, engrafted in an experimental model system, than either drug alone. In the coming months, they will verify these results and improve the schedule and dosing of the drugs and examine biomarkers that will help to identify the human breast tumors most likely to respond.

Mid-year Progress: Dr. D'Andrea's laboratory continues to evaluate the combination of bortezomib plus PARP inhibitor in preclinical breast tumor studies. They are examining the combination of two drugs in the treatment of triple negative breast cancer. They continue to verify previous results, to improve the schedule and dosing of the drugs in laboratory models bearing orthotopic implants of patient-derived tumors, and to examine biomarkers which identify those human breast tumors most likely to respond.

Bio:
A graduate of Harvard College, Dr. D'Andrea received his medical degree from Harvard Medical School in 1983. He completed his residency in Pediatrics at Children's Hospital of Philadelphia and a fellowship in pediatric hematology-oncology at Dana-Farber Cancer Institute (DFCI) and Children's Hospital, Boston. Dr. D'Andrea also completed a research fellowship at the Whitehead Institute of Biomedical Research at Massachusetts Institute of Technology where he cloned the receptor for erythropoietin while working in the laboratory of Dr. Harvey Lodish. Dr. D'Andrea joined the staff at DFCI in 1990. His research is focused on the molecular cause of human leukemia and breast cancer. He also investigates the pathogenesis of Fanconi anemia, a human genetic disease characterized by bone marrow failure and acute myeloid leukemia in children.

Dr. D'Andrea is internationally known for his research in the area of DNA damage and DNA repair. He is currently the Fuller-American Cancer Society Professor of Radiation Oncology at Harvard Medical School and the Chief of the Division of Genomic Stability and DNA Repair at DFCI. A recipient of numerous academic awards, Dr. D'Andrea is a former Stohlman Scholar of the Leukemia and Lymphoma Society (LLS) and has previously served on their Medical and Scientific Advisory Board. He is currently a member of the Career Development Selection Committee of the LLS. Dr. D'Andrea is the recipient of the 2001 E. Mead Johnson Award, the highest award in Pediatric Research, and is a Distinguished Clinical Investigator of the Doris Duke Charitable Trust.