Colorectal cancer models for novel drug discovery

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. Cla...

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Main Authors: Golovko, Daniel, Kedrin, Dmitriy, Yilmaz, Omer, Roper, Jatin
Other Authors: Massachusetts Institute of Technology. Department of Biology
Format: Article
Language:en_US
Published: Informa Healthcare 2016
Online Access:http://hdl.handle.net/1721.1/105874
https://orcid.org/0000-0001-6093-7282
https://orcid.org/0000-0002-7577-4612
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author Golovko, Daniel
Kedrin, Dmitriy
Yilmaz, Omer
Roper, Jatin
author2 Massachusetts Institute of Technology. Department of Biology
author_facet Massachusetts Institute of Technology. Department of Biology
Golovko, Daniel
Kedrin, Dmitriy
Yilmaz, Omer
Roper, Jatin
author_sort Golovko, Daniel
collection MIT
description 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.
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spelling mit-1721.1/1058742022-10-01T12:47:26Z Colorectal cancer models for novel drug discovery Golovko, Daniel Kedrin, Dmitriy Yilmaz, Omer Roper, Jatin Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT Kedrin, Dmitriy Yilmaz, Omer Roper, Jatin 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. United States. Department of Defense (Peer Reviewed Cancer Research Program Career Development Award CA120198) Tufts University. School of Medicine (Earl P. Charlton Fund Research Award) Tufts University. School of Medicine (Rozan Research Fund Pilot Award) V Foundation for Cancer Research (V Scholar Award) National Institutes of Health (U.S.) (Massachusetts General Hospital. Center for the Study of Inflammatory Bowl Diseases. Grant DK043351) National Institute on Aging (Grant NIA R00 AG04514) National Institutes of Health (U.S.) (Cancer Center Support Core Grant P30-CA14051) National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) (T32 Grant DK007191) 2016-12-19T18:54:17Z 2016-12-19T18:54:17Z 2015-08 Article http://purl.org/eprint/type/JournalArticle 1746-0441 1746-045X http://hdl.handle.net/1721.1/105874 Golovko, Daniel et al. “Colorectal Cancer Models for Novel Drug Discovery.” Expert Opinion on Drug Discovery 10.11 (2015): 1217–1229. https://orcid.org/0000-0001-6093-7282 https://orcid.org/0000-0002-7577-4612 en_US http://dx.doi.org/10.1517/17460441.2015.1079618 Expert Opinion on Drug Discovery Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Informa Healthcare PMC
spellingShingle Golovko, Daniel
Kedrin, Dmitriy
Yilmaz, Omer
Roper, Jatin
Colorectal cancer models for novel drug discovery
title Colorectal cancer models for novel drug discovery
title_full Colorectal cancer models for novel drug discovery
title_fullStr Colorectal cancer models for novel drug discovery
title_full_unstemmed Colorectal cancer models for novel drug discovery
title_short Colorectal cancer models for novel drug discovery
title_sort colorectal cancer models for novel drug discovery
url http://hdl.handle.net/1721.1/105874
https://orcid.org/0000-0001-6093-7282
https://orcid.org/0000-0002-7577-4612
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