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. 2015 May 9;15:381. doi: 10.1186/s12885-015-1360-4

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© Mortazavi et al. 2015

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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Cooperative disruption of signaling network downstream of mutated KRAS. Schematic view of KRAS/PAK1/Crk signaling pathway is demonstrated. Partial inhibition of KRAS signaling output by tolerable dose of prenylation inhibitors (i.e., FTI + GGTI) in addition to inhibition of a prominent KRAS effector (i.e., PAK1) result in dramatic anti-tumor effects. FTI: farnesyltransferase inhibitor, GGTI: geranylgeranyltransferase inhibitor, PAK1I: p21 associated kinase 1 inhibitor.