Review
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Pharmacol. Mar 9, 2015; 4(1): 47-57
Published online Mar 9, 2015. doi: 10.5497/wjp.v4.i1.47
Importance of microenvironment in preclinical models of breast and prostate cancer
Maija Valta, Katja Fagerlund, Mari Suominen, Jussi Halleen, Johanna Tuomela
Maija Valta, Johanna Tuomela, Department of Cell Biology and Anatomy, Institute of Biomedicine, University of Turku, 20520 Turku, Finland
Maija Valta, Division of Medicine, Turku University Hospital and University of Turku, 20520 Turku, Finland
Katja Fagerlund, Mari Suominen, Jussi Halleen, Johanna Tuomela, Pharmatest Services Ltd, Itäinen Pitkäkatu 4 C, 20520 Turku, Finland
Author contributions: Valta M, Fagerlund K, Suominen M, Halleen J and Tuomela J wrote the paper and they all meet the conditions 1, 2 and 3 proposed by the International Committee of Medical Journal Editors.
Supported by Eurostars program of Eureka (project acronym “D-SIST”).
Conflict-of-interest: No potential conflicts of interest relevant to this article were reported.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Johanna Tuomela, PhD, Adjunct Professor, Department of Cell Biology and Anatomy, Institute of Biomedicine, University of Turku, Kiinamyllynkatu 10, 20520 Turku, Finland. jomitu@utu.fi
Telephone: +358-50-4352677 Fax: +358-2-2784710
Received: August 31, 2014
Peer-review started: September 3, 2014
First decision: October 14, 2014
Revised: November 18, 2014
Accepted: January 15, 2015
Article in press: January 19, 2015
Published online: March 9, 2015
Abstract

The majority of cancer drugs entering clinical trials fail to reach the market due to poor efficacy. Preclinical efficacy has been traditionally tested using subcutaneous xenograft models that are cheap, fast and easy to perform. However, these models lack the correct tumor microenvironment, leading to poor clinical predictivity. Selecting compounds for clinical trials based on efficacy results obtained from subcutaneous xenograft models may therefore be one important reason for the high failure rates. In this review we concentrate in describing the role and importance of the tumor microenvironment in progression of breast and prostate cancer, and describe some breast and prostate cancer cell lines that are widely used in preclinical studies. We go through different preclinical efficacy models that incorporate the tissue microenvironment and should therefore be clinically more predictive than subcutaneous xenografts. These include three-dimensional cell culture models, orthotopic and metastasis models, humanized and transgenic mouse models, and patient-derived xenografts. Different endpoint measurements and applicable imaging techniques are also discussed. We conclude that models that incorporate the tissue microenvironment should be increasingly used in preclinical efficacy studies to reduce the current high attrition rates of cancer drugs in clinical trials.

Keywords: Tumor microenvironment, Breast cancer, Prostate cancer, Preclinical, Efficacy

Core tip: It is today a recognized major problem in cancer drug development that the vast majority of drugs entering clinical trials fail to reach the market due to poor efficacy. One important reason for this is the wide use of subcutaneous xenograft models that are cheap, fast and easy to perform, but lack tumor microenvironment. Concentrating on breast and prostate cancer, we explain why the presence of tumor microenvironment is important, and describe different types of preclinical efficacy models that incorporate tumor microenvironment. We state the importance of using these models to reduce the high failure rates in clinical trials.