Department News
Professor Fasan finds new means to "block" cancer cell growth
November 3, 2017
Fasan and coworkers have developed a new class of inhibitors against a notoriously challenging protein target implicated in the Hedgehog signaling pathway, one of the major cell signaling pathways found in human cells. This work, entitled “Design and Evolution of a Macrocyclic Peptide Inhibitor of the Sonic Hedgehog/Patched Interaction”, was recently published in the and soon after highlighted as a and in , the official magazine of the American Chemical Society, as well as shared by the .
The Hedgehog signaling pathway is active during embryonic development but it becomes quiescent in most adult tissues. In several forms of human cancer, however, this pathway is abnormally re-activated and this process provides a mechanism for cancer cells to support their own growth and promote migration to other tissues (metastasis). Using a peptide macrocyclization strategy previously developed in their lab, the Fasan group was able to design and develop a potent macrocyclic peptide inhibitor of Hedgehog proteins, the signaling molecules responsible for activation of this cellular pathway. These efforts have now given researchers a new tool to better understand the effect of Hedgehog signaling in cancer as well as a potential starting point for the development of new therapeutic agents against a range of human malignancies. This research was conducted by fourth-year graduate student Andrew Owens, former postdoc Ivan de Paola (now at Fresenius-Kabi), and former UR undergraduate student Yi-Wen (Amy) Liu (BS ’17, now at Cornell University).
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