Autophagy and TGF-Beta Antagonist Signaling in Breast Cancer Dormancy at Premetastatic Sites
Technical Report,01 May 2013,31 Mar 2015
Sloan-Kettering Institute for Cancer Research New York United States
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In this research project, we not only investigate fundamental questions about the biology of breast cancer metastasis, but also test our clinically-relevant hypothesis that targeting autophagy is a viable strategy for eradicating the disseminated breast cancer cells that are responsible for metastatic relapse, and that combined inhibition of autophagy and Coco can induce the death of dormant cells and prevent their reactivation. Over the two years of funding period, we have made notable progress, with all in vitro work accomplished and mouse modeling studies ongoing. Further, to translate this research into breast cancer treatment, the two laboratories involved in this project are also actively developing small molecule inhibitors targeting specific autophagy proteins and humanized antibodies blocking Coco and other players involved in reactivation of dormant legions. These inhibitors will be the drug leads for further medicinal chemistry and preclinicalclinical studies.