Colorectal cancer models for novel drug discovery.

Published

Journal Article (Review)

INTRODUCTION: Despite increased screening rates and advances in targeted therapy, colorectal cancer (CRC) remains the third leading cause of cancer-related mortality. CRC models that recapitulate key features of human disease are essential to the development of novel and effective therapeutics. Classic methods of modeling CRC such as human cell lines and xenograft mice, while useful for many applications, carry significant limitations. Recently developed in vitro and in vivo models overcome some of these deficiencies and thus can be utilized to better model CRC for mechanistic and translational research. AREAS COVERED: The authors review established models of in vitro cell culture and describe advances in organoid culture for studying normal and malignant intestine. They also discuss key features of classic xenograft models and describe other approaches for in vivo CRC research, including patient-derived xenograft, carcinogen-induced, orthotopic transplantation and transgenic mouse models. We also describe mouse models of metastatic CRC. EXPERT OPINION: No single model is optimal for drug discovery in CRC. Genetically engineered models overcome many limitations of xenograft models. Three-dimensional organoids can be efficiently derived from both normal and malignant tissue for large-scale in vitro and in vivo (transplantation) studies and are thus a significant advance in CRC drug discovery.

Full Text

Duke Authors

Cited Authors

  • Golovko, D; Kedrin, D; Yilmaz, ÖH; Roper, J

Published Date

  • 2015

Published In

Volume / Issue

  • 10 / 11

Start / End Page

  • 1217 - 1229

PubMed ID

  • 26295972

Pubmed Central ID

  • 26295972

Electronic International Standard Serial Number (EISSN)

  • 1746-045X

Digital Object Identifier (DOI)

  • 10.1517/17460441.2015.1079618

Language

  • eng

Conference Location

  • England