title: Colorectal cancer models for novel drug discovery.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors: a 1 Tufts Medical Center, Division of Gastroenterology and Molecular Oncology Research Institute , Boston, MA 02111, USA jroper@tuftsmedicalcenter.org.
authors: Daniel
authors: D
authors: Golovko
authors: b 2 MIT, The David H. Koch Institute for Integrative Cancer Research at MIT, Department of Biology , Cambridge, MA 02139, USA.|c 3 Massachusetts General Hospital and Harvard Medical School, Division of Gastroenterology , Boston, MA 02114, USA.
authors: Dmitriy
authors: D
authors: Kedrin
authors: b 2 MIT, The David H. Koch Institute for Integrative Cancer Research at MIT, Department of Biology , Cambridge, MA 02139, USA.|d 4 Massachusetts General Hospital and Harvard Medical School, Department of Pathology , Boston, MA 02114, USA.
authors: Ömer H
authors: ÖH
authors: Yilmaz
authors: a 1 Tufts Medical Center, Division of Gastroenterology and Molecular Oncology Research Institute , Boston, MA 02111, USA jroper@tuftsmedicalcenter.org.|b 2 MIT, The David H. Koch Institute for Integrative Cancer Research at MIT, Department of Biology , Cambridge, MA 02139, USA.
authors: Jatin
authors: J
authors: Roper
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D058990:Molecular Targeted Therapy; D057170:Translational Research, Biomedical / Q000379:methods; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents
keywords: colorectal cancer mouse models; intestinal organoid; patient-derived xenograft; transgenic colorectal cancer mouse model