William J. Gradishar, MD, FACP

Recent studies have identified a new type of breast cancer, the basal-like tumors, which have a poor prognosis and account for 15-20% of all breast cancer cases and 39% of cases in young African-American women. However, the genes responsible for their aggressive behavior are unknown. Basal-like tumors are clinically aggressive and lack targeted therapies because they are estrogen receptor (ER)-negative and HER2-negative. Dr. Gradishar and his colleagues have shown that turning off or "silencing" a cell stress protein called αB-crystallin in human basal-like breast cancer cells makes them more sensitive to chemotherapy drugs.

The Northwestern team has also examined the expression of αB-crystallin in breast tumors from women undergoing chemotherapy before surgery and found that breast tumors which expressed αB-crystallin responded poorly to chemotherapy compared to tumors which did not express this protein. These findings highlight the importance of developing new treatments for poor prognosis basal-like breast tumors, and they suggest that αB-crystallin may be a new drug target for these tumors.

In the coming year, Drs. Gradishar and Cryns will study the effects of turning off αB-crystallin on the ability of basal-like tumors to metastasize and to respond to chemotherapy in laboratory models. Their team will also screen large repositories or libraries of chemicals to identify drugs which make basal-like breast cancer cells expressing αB-crystallin more sensitive to chemotherapy. These studies will likely provide novel insights into the cause of basal-like breast cancer and may identify new drug candidates to treat these poor prognosis tumors.

Mid-Year Progress Report:
During the first few months of his current BCRF project, Drs. Gradishar and Cryns and colleagues have developed new laboratory models of basal-like breast cancer using fluorescently labeled breast cancer cells that can be visualized. Using this model, the Northwestern team is now examining whether silencing áB-crystallin blocks the growth and metastasis of basal-like tumors and makes them more susceptible to chemotherapy drugs. These studies will likely provide new molecular insights into the aggressive behavior of basal-like breast cancer and may lead to new treatment strategies.

Bio:
Dr. Gradishar is Professor of Medicine in the Division of Hematology and Medical Oncology, Department of Medicine, at the Feinberg School Medicine at Northwestern University in Chicago, Illinois, and a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. He also serves as Director of Breast Medical Oncology, Associate Director of the Lynn Sage Comprehensive Breast Program, and Program Director of Northwestern University's Hematology/Oncology Fellowship Training Program. His research focuses on the development of novel therapeutics for the treatment of breast cancer.

A Fellow of the American College of Physicians, Dr. Gradishar is also a member of the American Association for Cancer Research, the American Federation for Clinical Research, and the Association of Subspecialty Professors. He is the immediate past chair of the Oncology Training Program Committee of the American Society of Clinical Oncology (ASCO) as well as a member of ASCO's Program Committee. He is a member of the Breast Cancer Core Committee of the Eastern Cooperative Oncology Group, the Committee on Cancer of the American College of Surgeons, the National Comprehensive Cancer Network (NCCN) Breast Cancer Guidelines Panel, and the NCCN Breast Cancer Prevention Panel. In addition, he serves as a consultant to the Oncology Drug Advisory Committee of the FDA, serves on several study sections nationally and internationally including: NIH, Komen Foundation, Avon Foundation, American Cancer Society. Alberta Cancer Board and the Imperial Cancer Fund. He is a member of editorial boards and reviewer for numerous journals, including Journal of the National Cancer Institute, Journal of Clinical Oncology, and Clinical Cancer Research. He has published extensively in the area of breast cancer therapeutics, with a focus on new endocrine therapy, chemotherapy and novel targeted therapies.

Dr. Gradishar received his medical degree form the University of Illinois Abraham School of Medicine in Chicago. He completed a residency and chief residency in internal medicine at Michael Reese Hospital and Medical Center in Chicago and a fellowship in medical oncology at the University of Chicago.