Modeling RAS phenotype in colorectal cancer uncovers novel molecular traits of RAS dependency and improves prediction of response to targeted agents in patients.

ABSTRACT:

Purpose

KRAS wild-type status is an imperfect predictor of sensitivity to anti-EGF receptor (EGFR) monoclonal antibodies in colorectal cancer, motivating efforts to identify novel molecular aberrations driving RAS. This study aimed to build a quantitative readout of RAS pathway activity to (i) uncover molecular surrogates of RAS activity specific to colorectal cancer, (ii) improve the prediction of cetuximab response in patients, and (iii) suggest new treatment strategies.

Experimental design

A model of RAS pathway activity was trained in a large colorectal cancer dataset and validated in three independent colorectal cancer patient datasets. Novel molecular traits were inferred from The Cancer Genome Atlas colorectal cancer data. The ability of the RAS model to predict resis

SUBMITTER: Guinney J 

PROVIDER: S-EPMC4141655 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature