William J. Gradishar, MD, FACP

2009-2010 BCRF Project:
(made possible by generous support from The Housewares Charity Foundation)
Co-Investigator: Vincent L. Cryns, MD, Feinberg School of Medicine, Northwestern University

Basal-like tumors are a newly recognized type of breast cancer which are clinically aggressive and lack targeted therapies because they are estrogen receptor (ER)-negative and HER2-negative. Dr. Gradishar and colleagues have shown that a cell stress protein called áB-crystallin contributes to the aggressive behavior of basal-like tumors in part by making them resistant to chemotherapy.

During the past year, Dr. Gradishar and coworkers have developed new in vivo models of basal-like breast cancer using fluorescently labeled breast cancer cells. The team has shown that turning off ("silencing") the aB-crystallin gene blocks metastasis to the lungs, suggesting that aB-crystallin may be a promising drug target for anti-metastatic therapies. These in vivo models are currently being used to explore the molecular mechanisms of metastasis and to develop new treatments for basal-like tumors.

In the next year, Dr. Gradishar and his team will use these in vivo models to explore the molecular mechanisms of metastasis in basal-like breast cancer and to test promising therapies identified by the team. The researchers will also examine the prognostic value of aB-crystallin expression to predict brain metastasis and survival in women with breast cancer. In this way, these studies may lead to new prognostic biomarkers and treatments for poor prognosis basal-like breast tumors.

Mid-Year Progress Report:
Basal-like tumors are a newly recognized type of breast cancer (sometimes called "triple negative") which are clinically aggressive and lack targeted therapies because they are estrogen receptor (ER)-negative and HER2-negative. Dr. Gradishar and colleagues have shown that a cell stress protein called aB-crystallin contributes to the aggressive behavior of basal-like tumors in part by making them resistant to chemotherapy. More recently, Dr. Gradishar and coworkers have developed new in vivo models of basal-like breast cancer using fluorescently labeled breast cancer cells and shown that aB-crystallin promotes the spread ("metastasis") of breast cancer cells to distant organs.

During the current BCRF project period, Dr. Gradishar and his team have been exploring the molecular mechanisms by which aB-crystallin promotes metastasis in basal-like breast cancer and testing promising therapies identified by the team. The researchers are also examining the prognostic value of aB-crystallin expression to predict metastasis and survival in women with breast cancer. In this way, these studies may lead to new prognostic biomarkers and treatments for poor prognosis basal-like breast tumors.

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.