Characterization of an Oxaliplatin Sensitivity Predictor in a Preclinical Murine Model of Colorectal Cancer

Overview

Journal Mol Cancer Ther

Date 2012 Feb 22

PMID 22351745

Citations 22

Authors

Mickey K Kim

Takuya Osada

William T Barry

Xiao Yi Yang

Jennifer A Freedman

Katherine A Tsamis

Michael Datto

Bryan M Clary

Timothy Clay

Michael A Morse

Philip G Febbo

H Kim Lyerly

David S Hsu

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Chromatin Remodeling in Patient-Derived Colorectal Cancer Models.

Xiang K, Wang E, Mantyh J, Rupprecht G, Negrete M, Sanati G Adv Sci (Weinh). 2024; 11(16):e2303379.

PMID: 38380561 PMC: 11040356. DOI: 10.1002/advs.202303379.

Generation, evolution, interfering factors, applications, and challenges of patient-derived xenograft models in immunodeficient mice.

Zeng M, Ruan Z, Tang J, Liu M, Hu C, Fan P Cancer Cell Int. 2023; 23(1):120.

PMID: 37344821 PMC: 10283277. DOI: 10.1186/s12935-023-02953-3.

Protein Folding Stability Profiling of Colorectal Cancer Chemoresistance Identifies Functionally Relevant Biomarkers.

Quan B, Bailey M, Mantyh J, Hsu D, Fitzgerald M J Proteome Res. 2023; 22(6):1923-1935.

PMID: 37126456 PMC: 10441206. DOI: 10.1021/acs.jproteome.3c00045.

An autologous humanized patient-derived xenograft (PDX) model for evaluation of nivolumab immunotherapy in renal cell cancer: a case report.

Kang Y, Armstrong A, Hsu D Stem Cell Investig. 2022; 9:8.

PMID: 36393918 PMC: 9659479. DOI: 10.21037/sci-2022-029.

Leveraging patient derived models of FGFR2 fusion positive intrahepatic cholangiocarcinoma to identify synergistic therapies.

Lidsky M, Wang Z, Lu M, Liu A, Hsu S, McCall S NPJ Precis Oncol. 2022; 6(1):75.

PMID: 36274097 PMC: 9588766. DOI: 10.1038/s41698-022-00320-5.

References

Prewett M, Deevi D, Bassi R, Fan F, Ellis L, Hicklin D . Tumors established with cell lines selected for oxaliplatin resistance respond to oxaliplatin if combined with cetuximab. Clin Cancer Res. 2007; 13(24):7432-40. DOI: 10.1158/1078-0432.CCR-07-1768. View

Johnson W, Li C, Rabinovic A . Adjusting batch effects in microarray expression data using empirical Bayes methods. Biostatistics. 2006; 8(1):118-27. DOI: 10.1093/biostatistics/kxj037. View

Grothey A, Sargent D, Goldberg R, Schmoll H . Survival of patients with advanced colorectal cancer improves with the availability of fluorouracil-leucovorin, irinotecan, and oxaliplatin in the course of treatment. J Clin Oncol. 2004; 22(7):1209-14. DOI: 10.1200/JCO.2004.11.037. View

Bild A, Yao G, Chang J, Wang Q, Potti A, Chasse D . Oncogenic pathway signatures in human cancers as a guide to targeted therapies. Nature. 2005; 439(7074):353-7. DOI: 10.1038/nature04296. View

Shankavaram U, Reinhold W, Nishizuka S, Major S, Morita D, Chary K . Transcript and protein expression profiles of the NCI-60 cancer cell panel: an integromic microarray study. Mol Cancer Ther. 2007; 6(3):820-32. DOI: 10.1158/1535-7163.MCT-06-0650. View

Tournigand C, Andre T, Achille E, Lledo G, Flesh M, Mery-Mignard D . FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. J Clin Oncol. 2003; 22(2):229-37. DOI: 10.1200/JCO.2004.05.113. View

Perou C, Sorlie T, Eisen M, van de Rijn M, Jeffrey S, Rees C . Molecular portraits of human breast tumours. Nature. 2000; 406(6797):747-52. DOI: 10.1038/35021093. View

Buyse M, Thirion P, Carlson R, Burzykowski T, Molenberghs G, Piedbois P . Relation between tumour response to first-line chemotherapy and survival in advanced colorectal cancer: a meta-analysis. Meta-Analysis Group in Cancer. Lancet. 2000; 356(9227):373-8. DOI: 10.1016/s0140-6736(00)02528-9. View

Andre T, Bensmaine M, Louvet C, Francois E, Lucas V, Desseigne F . Multicenter phase II study of bimonthly high-dose leucovorin, fluorouracil infusion, and oxaliplatin for metastatic colorectal cancer resistant to the same leucovorin and fluorouracil regimen. J Clin Oncol. 1999; 17(11):3560-8. DOI: 10.1200/JCO.1999.17.11.3560. View

10.

Shipp M, Ross K, Tamayo P, Weng A, Kutok J, Aguiar R . Diffuse large B-cell lymphoma outcome prediction by gene-expression profiling and supervised machine learning. Nat Med. 2002; 8(1):68-74. DOI: 10.1038/nm0102-68. View

11.

Golub T . Genome-wide views of cancer. N Engl J Med. 2001; 344(8):601-2. DOI: 10.1056/NEJM200102223440809. View

12.

Golub T, Slonim D, Tamayo P, Huard C, Gaasenbeek M, Mesirov J . Molecular classification of cancer: class discovery and class prediction by gene expression monitoring. Science. 1999; 286(5439):531-7. DOI: 10.1126/science.286.5439.531. View

13.

Siddik Z . Cisplatin: mode of cytotoxic action and molecular basis of resistance. Oncogene. 2003; 22(47):7265-79. DOI: 10.1038/sj.onc.1206933. View

14.

Arnould S, Hennebelle I, Canal P, Bugat R, Guichard S . Cellular determinants of oxaliplatin sensitivity in colon cancer cell lines. Eur J Cancer. 2002; 39(1):112-9. DOI: 10.1016/s0959-8049(02)00411-2. View

15.

Rosenwald A, Wright G, Chan W, Connors J, Campo E, Fisher R . The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N Engl J Med. 2002; 346(25):1937-47. DOI: 10.1056/NEJMoa012914. View

16.

Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W . Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004; 350(23):2335-42. DOI: 10.1056/NEJMoa032691. View

17.

Shirota Y, Stoehlmacher J, Brabender J, Xiong Y, Uetake H, Danenberg K . ERCC1 and thymidylate synthase mRNA levels predict survival for colorectal cancer patients receiving combination oxaliplatin and fluorouracil chemotherapy. J Clin Oncol. 2001; 19(23):4298-304. DOI: 10.1200/JCO.2001.19.23.4298. View

18.

Park D, Zhang W, Stoehlmacher J, Tsao-Wei D, Groshen S, Gil J . ERCC1 gene polymorphism as a predictor for clinical outcome in advanced colorectal cancer patients treated with platinum-based chemotherapy. Clin Adv Hematol Oncol. 2005; 1(3):162-6. View

19.

Irizarry R, Bolstad B, Collin F, Cope L, Hobbs B, Speed T . Summaries of Affymetrix GeneChip probe level data. Nucleic Acids Res. 2003; 31(4):e15. PMC: 150247. DOI: 10.1093/nar/gng015. View

20.

Arango D, Wilson A, Shi Q, Corner G, Aranes M, Nicholas C . Molecular mechanisms of action and prediction of response to oxaliplatin in colorectal cancer cells. Br J Cancer. 2004; 91(11):1931-46. PMC: 2409767. DOI: 10.1038/sj.bjc.6602215. View