Common PIK3CA mutants and a novel 3' UTR mutation are associated with increased sensitivity to saracatinib.

ABSTRACT:

Purpose

Dysregulation of the phosphoinositide 3-kinase (PI3K) and Src signaling pathways commonly occur in colorectal cancer. Mutations in the PIK3CA gene are associated with an increase in severity of disease and worse clinical outcomes. Elevated levels of Src have been identified in premalignant lesions and are suggested to play a central role in tumor progression. Because these pathways appear to enhance tumor growth and metastasis, molecularly targeted agents for both pathways are currently being evaluated in early-phase clinical trials.

Experimental design

We used colorectal cancer cell lines and a patient-derived explant model to investigate the efficacy of saracatinib. Mutations in the PIK3CA were evaluated to examine the association between mutations in the PIK3CA ge

SUBMITTER: Arcaroli JJ 

PROVIDER: S-EPMC3836589 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature