Miniaturized pre-clinical cancer models as research and diagnostic tools

Adv Drug Deliv Rev. 2014 Apr:69-70:52-66. doi: 10.1016/j.addr.2013.11.010. Epub 2013 Dec 1.

Abstract

Cancer is one of the most common causes of death worldwide. Consequently, important resources are directed towards bettering treatments and outcomes. Cancer is difficult to treat due to its heterogeneity, plasticity and frequent drug resistance. New treatment strategies should strive for personalized approaches. These should target neoplastic and/or activated microenvironmental heterogeneity and plasticity without triggering resistance and spare host cells. In this review, the putative use of increasingly physiologically relevant microfabricated cell-culturing systems intended for drug development is discussed. There are two main reasons for the use of miniaturized systems. First, scaling down model size allows for high control of microenvironmental cues enabling more predictive outcomes. Second, miniaturization reduces reagent consumption, thus facilitating combinatorial approaches with little effort and enables the application of scarce materials, such as patient-derived samples. This review aims to give an overview of the state-of-the-art of such systems while predicting their application in cancer drug development.

Keywords: Body-on-a-chip; Cancer models; Cell adhesion-mediated drug resistance; Cell culturing devices; Combinatorial screening platforms; Extracellular matrix; Microfabricated model systems; Microfluidics; Pre-clinical drug assessment; Tumor microenvironment.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use
  • Biomedical Research / methods*
  • Biomedical Research / trends
  • Drug Discovery / methods
  • Drug Discovery / trends
  • Drug Evaluation, Preclinical / methods
  • Drug Evaluation, Preclinical / trends
  • Humans
  • Microfluidic Analytical Techniques / methods
  • Microfluidic Analytical Techniques / trends
  • Miniaturization / methods*
  • Models, Biological*
  • Neoplasms / diagnosis
  • Neoplasms / drug therapy*
  • Tumor Microenvironment* / drug effects
  • Tumor Microenvironment* / physiology

Substances

  • Antineoplastic Agents