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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
Seeking to improve outcomes in breast cancer by identifying aberrant cell processes that lead to tumor formation and progression.
Laboratory studies are conducted to test strategies to kill cancer stem cells by targeting a critical mediator of inflammation.
These studies could lead to new treatments for metastatic, basal-like/triple negative breast cancer.
Triple negative breast cancer (TNBC) is a subgroup of breast cancers that can be broken into other subgroups based on molecular characteristics. Some TNBC are more aggressive than others. Basal-like triple negative breast cancer is a particularly aggressive disease with a likelihood of spreading to other tissues – a process called metastasis. Drs. Gradishar and Cyrns have identified a protein that is driving part of this aggressive behavior. They are conducting laboratory studies to understand how it promotes metastasis for the development of new targeted therapies for patients with TNBC.
Full Research Summary
Basal-like tumors, which include those classified as triple negative, are clinically aggressive and lack targeted therapies.
Drs. Gradishar and Cryns and their colleagues have shown that a cell stress protein called alphaβ-crystallin contributes to the aggressive behavior of basal-like/triple negative tumors and regulates breast cancer metastasis to organs such as the brain.
Recently, the team showed that alphaβ-crystallin promotes survival of breast cancer stem cells (BCSC), specialized cells that are suspected to driver metastasis, suggesting that alphaβ-crystallin may be a target for stopping metastasis. It does this by increasing expression of a molecule called IL-6, a molecule involved in inflammatory response.
During the next year, the team will continue to examine the role of the alphaβ-crystallin/IL-6 network on BCSCs and metastasis and determine whether alphaβ-crystallin expression correlates with other markers of BCSCs. These studies could lead to new treatments for metastatic basal-like/triple negative breast cancer.
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.