University of Michigan
Ann Arbor, Michigan
Madeline & Sidney Forbes Professor of Oncology
Director, Forbes Institute for Cancer Discovery
Director Emeritus, Rogel Cancer Center
Understanding the potential role of breast cancer stem cells in cancer dormancy and recurrence.
Approximately 30 percent of breast cancer patients will experience a recurrence, and even patients diagnosed with early-stage breast cancer remain at risk years after their cancer is seemingly cleared. This may result from dormant cancer cells which can migrate to and reside in the bone marrow, only to become active again months or years later and form new tumors. More recently it has become apparent that tumors are composed of diverse communities of cells including cancer stem cells (CSCs), a subpopulation whose behavior allows them to initiate tumors, propagate metastasis, and contribute to treatment resistance. Dr. Wicha and his team are studying the role of CSCs in mediating tumor dormancy.
A major challenge in studying dormancy is recapturing it in laboratory experiments. The Wicha team, already leaders in cancer stem cell biology, developed experimental models that simulate the clinical scenario of dormant CSCs residing in bone marrow—a site that frequently harbors dormant cells in patients with breast cancer. Through this work, they generated laboratory models that mimic both short- and long-term dormancy.
The most common site of tumor recurrence is in the bone marrow, and Dr. Wicha and his team are studying how the bone marrow microenvironment regulates the dormancy of these cells and contributes to relapse when these metastatic cells escape dormancy. Using laboratory models as well as bone biopsies from patients with breast cancer, they will continue to investigate how the bone marrow microenvironment regulates dormancy as well as develop new strategies to target the metabolic and immunologic vulnerabilities of these dormant CSCs. The team’s goal is to develop safe treatments to eliminate these cells, preventing relapse and thus improve the long-term outcome for women with breast cancer.
Dr. Wicha received his MD degree from Stanford University School of Medicine in 1974, trained in Internal medicine at the University of Chicago and in Medical Oncology at the NIH. His scientific career has focused on the biology and treatment of breast cancer.
He has been a major leader in the science of cancer stem cells. His group was part of the team that first identified breast cancer stem cells, the first such cells identified in solid tumors. His laboratory has identified several cancer stem cell markers and developed in vitro and laboratory models to isolate and characterize these cells, models which have been widely utilized in the field. His group has subsequently elucidated several intrinsic and extrinsic pathways which regulate stem cell self-renewal and cell fate decisions. This work has directly led to the development of several clinical trials aimed at targeting breast cancer stem cells.
Dr. Wicha is also the founding director of the University of Michigan Rogel Cancer Center, a position he held for 27 years. Under his leadership, the Rogel Cancer Center established itself as one of the nation’s premier cancer centers. In 2015, Dr. Wicha stepped down as the Cancer Center Director enabling him to devote his full efforts to cancer stem cell research. He now holds the Madeline and Sidney Forbes Professor of Oncology Chair and serves as Director of the Forbes Institute for Cancer Discovery. He was appointed by President Obama to the National Cancer Advisory Board (NCAB). This board advises the NCI Director and Secretary of Health on matters related to cancer research and health policy.
In work supported by BCRF, we have identified an important role for metabolic regulation and the innate immune system in regulating cancer stem cell dormancy.
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