William J. Gradishar, MD, FACP
Director, Breast Medical Oncology
Professor of Medicine
Robert H. Lurie Comprehensive Cancer Center
Northwestern University Feinberg School of Medicine
2013-2014 BCRF Project:
(The Housewares Charity Foundation Award)
Co-Investigator: Vincent L. Cryns, MD, University of Wisconsin, Madison, WI
Basal-like tumors are clinically aggressive and lack targeted therapies because they are estrogen receptor (ER)-negative and HER2-negative. Dr. Cryns and colleagues have shown that a cell stress protein called αB-crystallin contributes to the aggressive behavior of basal-like tumors. More recently, they have developed new in vivo models of basal-like breast cancer that spread (“metastasize”) from the breast to the brain and other organs. Using these in vivo models, the researchers have demonstrated that αB-crystallin is a key regulator of breast cancer metastasis. In 2012-2013, they created a new genetic model of breast cancer and demonstrated that deleting the αB-crystallin gene inhibits lung metastasis. The team has also demonstrated that reducing the expression of αB-crystallin may make cancer cells more sensitive to chemotherapy and some targeted therapies. Finally, they have identified proteins that interact with αB-crystallin and are determining the potential role of these proteins in metastasis. These studies provide novel insights into the molecular mechanisms of basal-like breast cancer and point to αB-crystallin as a promising drug target in these poor-prognosis breast tumors.
Basal-like tumors are clinically aggressive and lack targeted therapies because they are estrogen receptor (ER)-negative and HER2-negative. Dr. Cryns and colleagues have shown that a cell stress protein called αB-crystallin contributes to the aggressive behavior of basal-like tumors. More recently, Dr. Cryns and his team have developed new in vivo models of basal-like breast cancer and shown that αB-crystallin regulates the spread (“metastasis”) of breast tumor cells to the brain and other organs. During the current year of BCRF funding, the researchers are investigating the mechanisms by which αB-crystallin promotes metastasis and screening for drugs to block the expression of this protein.
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.