Betsy Bramsen Professor of Breast Oncology
Director, Maggie Daley Center for Women’s Cancer Care
Robert H. Lurie Comprehensive Cancer Center
Feinberg School of Medicine
Improving outcomes in breast cancer by identifying aberrant cell processes that lead to tumor formation and progression.
Basal-like triple-negative breast cancers are aggressive and lack targeted therapies because they do not depend on the estrogen or progesterone hormones or HER2 for growth, hence the term “triple-negative.” Drs. Gradishar and Cryns are studying cell stress proteins called αβ-crystallin and Hsp27, which interact with cancer-promoting proteins and contribute to the aggressive behavior of basal-like/triple-negative breast cancer (TNBC) by. They have shown that αβ-crystallin and Hsp27 interact with a mutant form of p53, the most commonly mutated gene in cancer, and link p53 to Akt, a growth-promoting protein that is often upregulated in cancer. Their work may lead to the identification of new approaches to target oncogenes in a broad spectrum of breast tumors.
The team has discovered that mutant p53 depends on αβ-crystallin and Hsp27 to promote tumor formation. Over the past year, they have identified the mechanisms by which p53 and Akt are regulated by these proteins and how the p53 and Akt cancer pathways are linked. The team also discovered that αβ-crystallin and Hsp27 each directly bind and regulate other key cancer drivers to promote tumor growth. Finally, Drs. Gradishar and Cryns determined that blocking αβ-crystallin and Hsp27 triggers tumor cells to die. These findings could lead to fundamentally new treatment approaches for TNBC.
In the coming year, Drs. Gradishar and Cryns will use genetic approaches to block αβ-crystallin and Hsp27 and examine how this affects the activity and function of multiple cancer drivers including p53, Akt, and others—especially their ability to promote tumor growth and chemotherapy resistance. They will also examine whether other cell stress proteins play a similar role in tumor-promoting pathways.
William J. Gradishar is Betsy Bramsen Professor of Breast Oncology in the Division of Hematology and Medical Oncology at the Feinberg School Medicine at Northwestern University and a member of the Robert H. Lurie Comprehensive Cancer Center. He is Director of the Maggie Daley Center for Women’s Cancer Care. He has been Chair of the Annual Lynn Sage Breast Cancer Symposium since its inception. 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 past chair of the Oncology Training Program Committee and Communications Committee of the American Society of Clinical Oncology (ASCO). He is Chair-elect of the ASCO Professional Development Committee and a member of ASCO’s Scientific Program Committee. He is a member of the Breast Cancer Core Committee and Co-Chair of the Developmental Therapeutics Working Group 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. He also serves as a consultant to the Oncology Drug Advisory Committee of the FDA. He has served on numerous study sections and is a member of the editorial boards for the Journal of Clinical Oncology, Oncology, Clinical Breast Cancer, Journal Watch, European Journal of Clinical and Medical Oncology, and Clinical Cancer Research.
The Housewares Charity Foundation Award
University of Wisconsin
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