Characterization of an oxaliplatin sensitivity predictor in a preclinical murine model of colorectal cancer.

Published

Journal Article

Despite advances in contemporary chemotherapeutic strategies, long-term survival still remains elusive for patients with metastatic colorectal cancer. A better understanding of the molecular markers of drug sensitivity to match therapy with patient is needed to improve clinical outcomes. In this study, we used in vitro drug sensitivity data from the NCI-60 cell lines together with their Affymetrix microarray data to develop a gene expression signature to predict sensitivity to oxaliplatin. To validate our oxaliplatin sensitivity signature, patient-derived colorectal cancer explants (PDCCE) were developed in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice from resected human colorectal tumors. Analysis of gene expression profiles found similarities between the PDCCEs and their parental human tumors, suggesting their utility to study drug sensitivity in vivo. The oxaliplatin sensitivity signature was then validated in vivo with response data from 14 PDCCEs treated with oxaliplatin and was found to have an accuracy of 92.9% (sensitivity = 87.5%; specificity = 100%). Our findings suggest that PDCCEs can be a novel source to study drug sensitivity in colorectal cancer. Furthermore, genomic-based analysis has the potential to be incorporated into future strategies to optimize individual therapy for patients with metastatic colorectal cancer.

Full Text

Duke Authors

Cited Authors

  • Kim, MK; Osada, T; Barry, WT; Yang, XY; Freedman, JA; Tsamis, KA; Datto, M; Clary, BM; Clay, T; Morse, MA; Febbo, PG; Lyerly, HK; Hsu, DS

Published Date

  • July 2012

Published In

Volume / Issue

  • 11 / 7

Start / End Page

  • 1500 - 1509

PubMed ID

  • 22351745

Pubmed Central ID

  • 22351745

Electronic International Standard Serial Number (EISSN)

  • 1538-8514

International Standard Serial Number (ISSN)

  • 1535-7163

Digital Object Identifier (DOI)

  • 10.1158/1535-7163.MCT-11-0937

Language

  • eng