|  Help  |  About  |  Contact Us

Publication : RHOA-FAK is a required signaling axis for the maintenance of KRAS-driven lung adenocarcinomas.

First Author  Konstantinidou G Year  2013
Journal  Cancer Discov Volume  3
Issue  4 Pages  444-57
PubMed ID  23358651 Mgi Jnum  J:198243
Mgi Id  MGI:5495894 Doi  10.1158/2159-8290.CD-12-0388
Citation  Konstantinidou G, et al. (2013) RHOA-FAK is a required signaling axis for the maintenance of KRAS-driven lung adenocarcinomas. Cancer Discov 3(4):444-57
abstractText  Non-small cell lung cancer (NSCLC) often expresses mutant KRAS together with tumor-associated mutations of the CDKN2A locus, which are associated with aggressive, therapy-resistant tumors. Here, we unravel specific requirements for the maintenance of NSCLC that carries this genotype. We establish that the extracellular signal-regulated kinase (ERK)/RHOA/focal adhesion kinase (FAK) network is deregulated in high-grade lung tumors. Suppression of RHOA or FAK induces cell death selectively in mutant KRAS;INK4A/ARF-deficient lung cancer cells. Furthermore, pharmacologic inhibition of FAK caused tumor regression specifically in the high-grade lung cancer that developed in mutant Kras;Cdkn2a-null mice. These findings provide a rationale for the rapid implementation of genotype-specific targeted therapies using FAK inhibitors in patients with cancer. SIGNIFICANCE: Targeted therapies are effective for only a small fraction of patients with cancer. We report that FAK inhibitors exert potent antitumor effects in NSCLCs that express mutant KRAS in association with INK4A/ARF deficiency. These results reveal a novel genotype-specific vulnerability of cancer cells that can be exploited for therapeutic purposes.
Quick Links:
 
Quick Links:
 

Expression

Publication --> Expression annotations

 

Other

11 Bio Entities

Trail: Publication

0 Expression