Posted July 30, 2013
Charles Landen, M.D., University of Alabama at Birmingham
The cancer stem cell hypothesis suggests that a subset of cells has the ability to initiate tumors, metastasize, and survive treatment. Department of Defense Ovarian Cancer Research Program Ovarian Cancer Academy member Dr. Landen is intrigued by these cells, noting "The clinical course of ovarian cancer fits this paradigm. Most patients even with advanced disease will have an outstanding initial response to chemotherapy, even to the point where no disease is detectable by blood test, imaging, or direct examination with surgery. However, even in the patients with strong initial responses, the majority will later develop recurrence with chemoresistant disease, leading us to believe that a very small portion of tumor cells have mechanisms in place that allow them to survive, lie dormant, and later regrow. If we can identify these cells and how they survive, it will significantly change our strategies on how to eliminate all cancer cells, not just the majority." Dr. Landen is studying this hypothesis using several approaches, including analysis of stem cell signaling pathways, examination of patient samples prior to therapy as compared to with recurrence, and direct implantation of tumors into mice so that responses of heterogeneous tumors to chemotherapy can be studied in a more controlled setting. Thus far, they have demonstrated that targeting either the Hedgehog pathway or the TGF-ß co-receptor endoglin leads to enhanced ability of chemotherapeutic agents to kill chemoresistant cancer cells. Clinical trials to test these agents in patients are now under development. As a clinician, Dr. Landen is constantly inspired by his patients, and is active in advocacy, serving on the Board of Directors for the Norma Livingston Foundation in Birmingham and the national Foundation for Women's Cancer. He says "We feel honored to be supported by the Department of Defense, given their history of considering patient advocates in their review process, and focusing on approaches that not only shed light onto the biology of disease, but also can ultimately lead to patient benefit."
Steg AD, Bevis KS, Katre AA, Ziebarth A, Dobbin ZC, Alvarez RD, Zhang K, Conner M, and Landen CN. 2012. Stem cell pathways contribute to clinical chemoresistance in ovarian cancer. Clinical Cancer Research 18(3):869-881.
Steg AD, Katre AA, Bevis KS, Ziebarth A, Dobbin ZC, Shah MM, Alvarez RD, and Landen CN. 2012. Smoothened antagonists reverse taxane resistance in ovarian cancer. Molecular Cancer Therapeutics 11(7):1587-1597.
Ziebarth A, Nowsheen S, Steg AD, Shah MM, Katre AA, Dobbin ZC, Hood HD, Lopex-Berestein G, Sood AK, Conner M, Yang ES, and Landen CN. 2013. Endoglin (CD105) contributes to platinum resistance and is a target for tumor-specific therapy in epithelial ovarian cancer. Clinical Cancer Research 19(1):170-182.