Two large federal grants received this summer will allow researchers at the James P. Wilmot Cancer Center to continue their work into stem cells that give rise to cancer.
Wei Hsu, Ph.D., an associate professor of Biomedical Genetics and Oncology at the University of Rochester Medical Center, was awarded $1.5 million from the National Cancer Institute for a five-year breast cancer stem cell project.
Michael Becker, M.D., an assistant professor of Medicine at URMC, received $240,000 from the National Institutes of Health for a two-year investigation into the clinical relevance of stem cells involved in acute leukemia.
Wilmot Cancer Center researchers are leaders in exploring the provocative idea that mutations at the stem cell level fuel cancer and tumor formation. This hypothesis might explain why cancer often cannot be entirely wiped out by modern therapy, because no current treatment reaches the stem cell, or the origin of the disease. Thus the goal is to investigate pathways and molecular networks that control cancer stem cells, with hope that a better understanding could lead to a new generation of therapies.
Hsu’s team has been investigating how stem cells contribute to breast development, from the embryonic stage through puberty and pregnancy. His laboratory is particularly interested in how pregnancy alters the breast stem cells and whether these changes have any affect on breast cancer.
Many studies have shown a link between reproductive history and breast cancer; women who have never been pregnant or who have their first child after age 35 are believed to be at increased risk of breast cancer. Some evidence suggests that breast cells are remodeled during pregnancy and lactation, Hsu said, and it is easy to imagine that remodeled cells might be more resistant to cancer.
On the other hand, pregnancy-induced hormones such as estrogen also might alter the stem cell population in the breast and play a role in tumor development. Hsu’s laboratory has developed powerful tools – a unique genetic mouse model and a stem cell culture system – that will help researchers explore what happens to breast cells during these crucial periods of development and what, in fact, promotes tumor growth.
While Hsu’s research is still too early to have a direct impact on patients, Becker’s study involves assessing the clinical relevance of leukemia stem cells (LSCs) to patients undergoing therapy for acute myelocytic leukemia. A decade ago scientists discovered the first evidence of LSCs, and since then have come to believe that this subset of cells is responsible for maintaining the disease. Yet the research has not progressed much beyond the laboratory. Becker’s goal is to study several properties of LSCs in patients during all stages of treatment and determine if these properties remain stable or change. He has initiated a multi-center study to obtain patient cell samples before treatment begins, following treatment, and at the time of relapse.
Data from the study is expected to represent the first major step in establishing the clinical relevance of the cancer stem cell model for this disease, which is the most common type of leukemia among adults and has a very poor prognosis. The ultimate goal is to identify which pathways have the most potential to kill the minimal residual disease that is left to proliferate even after aggressive therapy.
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