Current and future horizons of patient-derived xenograft models in colorectal cancer translational research

Akira Inoue, Angela K. Deem, Scott Kopetz, Timothy P. Heffernan, Giulio F. Draetta, Alessandro Carugo

Research output: Contribution to journalReview article

Abstract

Our poor understanding of the intricate biology of cancer and the limited availability of preclinical models that faithfully recapitulate the complexity of tumors are primary contributors to the high failure rate of novel therapeutics in oncology clinical studies. To address this need, patientderived xenograft (PDX) platforms have been widely deployed and have reached a point of development where we can critically review their utility to model and interrogate relevant clinical scenarios, including tumor heterogeneity and clonal evolution, contributions of the tumor microenvironment, identification of novel drugs and biomarkers, and mechanisms of drug resistance. Colorectal cancer (CRC) constitutes a unique case to illustrate clinical perspectives revealed by PDX studies, as they overcome limitations intrinsic to conventional ex vivo models. Furthermore, the success of molecularly annotated "Avatar" models for co-clinical trials in other diseases suggests that this approach may provide an additional opportunity to improve clinical decisions, including opportunities for precision targeted therapeutics, for patients with CRC in real time. Although critical weaknesses have been identified with regard to the ability of PDX models to predict clinical outcomes, for now, they are certainly the model of choice for preclinical studies in CRC. Ongoing multi-institutional efforts to develop and share large-scale, well-annotated PDX resources aim to maximize their translational potential. This review comprehensively surveys the current status of PDX models in translational CRC research and discusses the opportunities and considerations for future PDX development.

Original languageEnglish (US)
Article number1321
JournalCancers
Volume11
Issue number9
DOIs
StatePublished - Sep 2019

Fingerprint

Translational Medical Research
Heterografts
Colorectal Neoplasms
Clonal Evolution
Neoplasms
Tumor Microenvironment
Drug Resistance
Biomarkers
Clinical Trials
Therapeutics
Research
Pharmaceutical Preparations

Keywords

  • Avatar models
  • Co-clinical trials
  • Drug development
  • Humanized mice
  • Precision medicine

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Current and future horizons of patient-derived xenograft models in colorectal cancer translational research. / Inoue, Akira; Deem, Angela K.; Kopetz, Scott; Heffernan, Timothy P.; Draetta, Giulio F.; Carugo, Alessandro.

In: Cancers, Vol. 11, No. 9, 1321, 09.2019.

Research output: Contribution to journalReview article

Inoue, Akira ; Deem, Angela K. ; Kopetz, Scott ; Heffernan, Timothy P. ; Draetta, Giulio F. ; Carugo, Alessandro. / Current and future horizons of patient-derived xenograft models in colorectal cancer translational research. In: Cancers. 2019 ; Vol. 11, No. 9.
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