Development of a colon cancer GEMM-derived orthotopic transplant model for drug discovery and validation.

ABSTRACT:

Purpose

Effective therapies for KRAS-mutant colorectal cancer (CRC) are a critical unmet clinical need. Previously, we described genetically engineered mouse models (GEMM) for sporadic Kras-mutant and non-mutant CRC suitable for preclinical evaluation of experimental therapeutics. To accelerate drug discovery and validation, we sought to derive low-passage cell lines from GEMM Kras-mutant and wild-type tumors for in vitro screening and transplantation into the native colonic environment of immunocompetent mice for in vivo validation.

Experimental design

Cell lines were derived from Kras-mutant and non-mutant GEMM tumors under defined media conditions. Growth kinetics, phosphoproteomes, transcriptomes, drug sensitivity, and metabolism were examined. Cell lines were implanted

SUBMITTER: Martin ES 

PROVIDER: S-EPMC3951107 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature