| Literature DB >> 22874768 |
Fred Harbinski1, Vanessa J Craig, Sneha Sanghavi, Douglas Jeffery, Lijuan Liu, Kelly Ann Sheppard, Sabrina Wagner, Christelle Stamm, Andreas Buness, Christian Chatenay-Rivauday, Yao Yao, Feng He, Chris X Lu, Vito Guagnano, Thomas Metz, Peter M Finan, Francesco Hofmann, William R Sellers, Jeffrey A Porter, Vic E Myer, Diana Graus-Porta, Christopher J Wilson, Alan Buckler, Ralph Tiedt.
Abstract
The overall power of kinase inhibitors is substantially overshadowed by the acquisition of drug resistance. To address this issue, we systematically assessed the potential of secreted proteins to induce resistance to kinase inhibitors. To this end, we developed a high-throughput platform for screening a cDNA library encoding 3,432 secreted proteins in cellular assays. Using cancer cells originally dependent on either MET, FGFR2, or FGFR3, we observed a bypass of dependence through ligand-mediated activation of alternative receptor tyrosine kinases (RTK). Our findings indicate a broad and versatile potential for RTKs from the HER and FGFR families as well as MET to compensate for loss of each other. We further provide evidence that combined inhibition of simultaneously active RTKs can lead to an added anticancer effect.Entities:
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Year: 2012 PMID： 22874768 DOI： 10.1158/2159-8290.CD-12-0237
Source DB: PubMed Journal: Cancer Discov ISSN： 2159-8274 Impact factor: 39.397