William J. Gradishar, MD, FACP
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 don’t depend on the estrogen or progesterone hormones or HER2 for growth, hence the term “triple-negative.” Drs. Cryns and Gradishar are studying a cell stress protein called αβ-crystallin, which contributes to the aggressive behavior of basal-like/triple-negative breast cancer (TNBC) by interacting with cancer-promoting proteins. They have shown that it interacts with a mutant form of p53, the most commonly mutated gene in cancer, and links 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 to promote tumor formation. In addition, they identified a promising drug that reduces αβ-crystallin levels in breast cancer cells, and they plan to test this drug and related ones in TNBC models. Their findings could lead to completely new strategies to target and treat aggressive TNBC.
In the coming year, Drs. Cryns and Gradishar aim to delineate the effects of inhibiting αβ-crystallin on the stability of mutant p53 and on the activation of Akt. They hypothesize that without αβ-crystallin, mutant p53 will not be able to function, Akt will not be activated and be able to promote tumor growth, and breast cancer cells will die. The team will also determine whether inhibiting αβ-crystallin affects oncogenic transformation and tumor progression that is mediated by mutant p53.
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 board for the Journal of Clinical Oncology, Oncology, Clinical Breast Cancer, Journal Watch, European Journal of Clinical and Medical Oncology and Clinical Cancer Research.
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