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

Publication ,  Journal Article
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 in: Mol Cancer Ther
July 2012

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.

Duke Scholars

Published In

Mol Cancer Ther

DOI

EISSN

1538-8514

Publication Date

July 2012

Volume

11

Issue

7

Start / End Page

1500 / 1509

Location

United States

Related Subject Headings

  • Transplantation, Heterologous
  • Prognosis
  • Oxaliplatin
  • Organoplatinum Compounds
  • Oncology & Carcinogenesis
  • Mice
  • Humans
  • Gene Expression Regulation, Neoplastic
  • Gene Expression Profiling
  • Disease Models, Animal
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Kim, M. K., Osada, T., Barry, W. T., Yang, X. Y., Freedman, J. A., Tsamis, K. A., … Hsu, D. S. (2012). Characterization of an oxaliplatin sensitivity predictor in a preclinical murine model of colorectal cancer. Mol Cancer Ther, 11(7), 1500–1509. https://doi.org/10.1158/1535-7163.MCT-11-0937
Kim, Mickey K., Takuya Osada, William T. Barry, Xiao Yi Yang, Jennifer A. Freedman, Katherine A. Tsamis, Michael Datto, et al. “Characterization of an oxaliplatin sensitivity predictor in a preclinical murine model of colorectal cancer.Mol Cancer Ther 11, no. 7 (July 2012): 1500–1509. https://doi.org/10.1158/1535-7163.MCT-11-0937.
Kim MK, Osada T, Barry WT, Yang XY, Freedman JA, Tsamis KA, et al. Characterization of an oxaliplatin sensitivity predictor in a preclinical murine model of colorectal cancer. Mol Cancer Ther. 2012 Jul;11(7):1500–9.
Kim, Mickey K., et al. “Characterization of an oxaliplatin sensitivity predictor in a preclinical murine model of colorectal cancer.Mol Cancer Ther, vol. 11, no. 7, July 2012, pp. 1500–09. Pubmed, doi:10.1158/1535-7163.MCT-11-0937.
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. Characterization of an oxaliplatin sensitivity predictor in a preclinical murine model of colorectal cancer. Mol Cancer Ther. 2012 Jul;11(7):1500–1509.

Published In

Mol Cancer Ther

DOI

EISSN

1538-8514

Publication Date

July 2012

Volume

11

Issue

7

Start / End Page

1500 / 1509

Location

United States

Related Subject Headings

  • Transplantation, Heterologous
  • Prognosis
  • Oxaliplatin
  • Organoplatinum Compounds
  • Oncology & Carcinogenesis
  • Mice
  • Humans
  • Gene Expression Regulation, Neoplastic
  • Gene Expression Profiling
  • Disease Models, Animal