A systems biology approach identifies SART1 as a novel determinant of both 5-fluorouracil and SN38 drug resistance in colorectal cancer.

ABSTRACT: Chemotherapy response rates for advanced colorectal cancer remain disappointingly low, primarily because of drug resistance, so there is an urgent need to improve current treatment strategies. To identify novel determinants of resistance to the clinically relevant drugs 5-fluorouracil (5-FU) and SN38 (the active metabolite of irinotecan), transcriptional profiling experiments were carried out on pretreatment metastatic colorectal cancer biopsies and HCT116 parental and chemotherapy-resistant cell line models using a disease-specific DNA microarray. To enrich for potential chemoresistance-determining genes, an unsupervised bioinformatics approach was used, and 50 genes were selected and then functionally assessed using custom-designed short interfering RNA (siRNA) screens. In the primary si

SUBMITTER: Allen WL 

PROVIDER: S-EPMC3272421 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature