Targeting SRC Family Kinases in HSP90 in Lung Cancer
Technical Report,30 Sep 2014,29 Sep 2015
Institute for Cancer Research Philadelphia United States
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Lung cancer has the highest mortality rate of all cancers in the United States and has adversely affected the lives of many Americans. Typically, only 16 of patients survive 5 years beyond initial diagnosis. The goal of this proposal is to try to improve application of a drug, dasatinib, which has some promise for lung cancer treatment. Dasatinib is a targeted drug, with action that involves blocking the function of a group of proteins defined as the Src group whose action is important in lung cancer metastasis. In our study, we have been testing whether the action of dasatinib in lung cancer is enhanced by combining it with a second agent, ganetespib, that targets Src and other pro-cancerous proteins by an alternative mechanism. We have also been evaluating whether cellular status of a protein, NEDD9, that we have shown to bind directly to Src, influences the activity of dasatinib. Using in vivo analysis, experiments in progress are indicating that mice lacking NEDD9 are greatly sensitized to dasatinib but not ganetespib, and that mice lacking NEDD9 develop more aggressive lung cancers than those with intactNEDD9 while the dasatinibganetespib combination does not improve the efficacy of dasatinib.