Tissue-engineered models of human tumors for cancer research

Expert Opin Drug Discov. 2015 Mar;10(3):257-68. doi: 10.1517/17460441.2015.1009442. Epub 2015 Feb 7.

Abstract

Introduction: Drug toxicity often goes undetected until clinical trials, which are the most costly and dangerous phase of drug development. Both the cultures of human cells and animal studies have limitations that cannot be overcome by incremental improvements in drug-testing protocols. A new generation of bioengineered tumors is now emerging in response to these limitations, with potential to transform drug screening by providing predictive models of tumors within their tissue context, for studies of drug safety and efficacy. An area that could greatly benefit from these models is cancer research.

Areas covered: In this review, the authors first describe the engineered tumor systems, using Ewing's sarcoma as an example of human tumor that cannot be predictably studied in cell culture and animal models. Then, they discuss the importance of the tissue context for cancer progression and outline the biomimetic principles for engineering human tumors. Finally, they discuss the utility of bioengineered tumor models for cancer research and address the challenges in modeling human tumors for use in drug discovery and testing.

Expert opinion: While tissue models are just emerging as a new tool for cancer drug discovery, they are already demonstrating potential for recapitulating, in vitro, the native behavior of human tumors. Still, numerous challenges need to be addressed before we can have platforms with a predictive power appropriate for the pharmaceutical industry. Some of the key needs include the incorporation of the vascular compartment, immune system components, and mechanical signals that regulate tumor development and function.

Keywords: bioengineered tumors; biomimetics; bone tumors; drug discovery; microenvironment; tissue engineering; vascularization.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Agents / toxicity
  • Disease Progression
  • Drug Design
  • Drug Discovery / methods*
  • Humans
  • Models, Biological
  • Neoplasms / pathology*
  • Tissue Engineering*

Substances

  • Antineoplastic Agents