The AACR Judah Folkman Career Development Award for Anti-Angiogenesis Research is open to junior faculty who completed postdoctoral studies or clinical fellowships no more than three years prior to the start of the grant term; who are in their first full-time, faculty appointment and hold the title of instructor, research assistant professor, assistant professor or an equivalent full-time faculty appointment; and who are at an academic, medical or research Institution. Research projects are restricted to basic, clinical, translational or epidemiological projects that substantially advance the field of anti-angiogenesis research in cancer.
2010 GRANTEE
Marco Seandel, M.D., Ph.D.Assistant Professor of Cell and Development Biology, Joan & Stanford I. Weill Medical College of Cornell University, New York, NY
Blocking Endothelial Trophic Support of Chemoresistant Genitourinary Tumors
"Conventional anti-angiogenic therapy (aimed at blocking tumor blood vessel growth) has met with only limited success in the clinic. However, it has been shown recently that endothelial cells (ECs), as the cellular components of the blood vessels, do not merely perform a structural role but actually send signals to surrounding cells. The endothelial-derived signals transmitted to cancer cells that support tumor growth are poorly understood and are a major subject of our interests. This project explores the concept that blood vessels provide trophic support (or nutrition) to subsets of tumor cells via secreted and cell surface proteins. Targeting these interactions could yield novel therapeutic strategies. A major technical barrier to the elucidation of such signals, however, is that ECs cannot be grown without special additives (i.e., serum and growth factors) that themselves directly affect tumor growth and interfere with detection of novel signals. We have overcome this obstacle by employing ECs that have been slightly altered through delivery of the adenoviral E4ORF1 gene while remaining otherwise nearly indistinguishable from natural ECs. The experiments underway examine the way ECs support genitourinary tumors and also protect them from chemotherapy, as modeled in vitro and also using an animal model. The functional significance of candidate pathways (e.g., the NF-κappaB signaling pathway) identified in preliminary studies will be examined in detail in ECs using genetic and chemical tools. In the future, we hope that therapeutic targeting of signals between ECs and the tumor will constitute a new and effective way to eliminate the residual cancer that almost inevitably remains after optimal treatment. It is an exceptional honor to be awarded the AACR Judah Folkman Career Development Award for Anti-Angiogenesis Research, which will be critical to moving my research forward. Dr. Folkman was a great source of personal inspiration to me, during my graduate student and postdoctoral years, and I am truly humbled to be linked in this way to such a pioneering and monumental figure in the history of cancer research."
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