In vitro models of tumor vessels and matrix: engineering approaches to investigate transport limitations and drug delivery in cancer

Adv Drug Deliv Rev. 2014 Apr;69-70:205-216. doi: 10.1016/j.addr.2013.11.011. Epub 2013 Dec 2.


Tumor-stroma interactions have emerged as critical determinants of drug efficacy. However, the underlying biological and physicochemical mechanisms by which the microenvironment regulates therapeutic response remain unclear, due in part to a lack of physiologically relevant in vitro platforms to accurately interrogate tissue-level phenomena. Tissue-engineered tumor models are beginning to address this shortcoming. By allowing selective incorporation of microenvironmental complexity, these platforms afford unique access to tumor-associated signaling and transport dynamics. This review will focus on engineering approaches to study drug delivery as a function of tumor-associated changes of the vasculature and extracellular matrix (ECM). First, we review current biological understanding of these components and discuss their impact on transport processes. Then, we evaluate existing microfluidic, tissue engineering, and materials science strategies to recapitulate vascular and ECM characteristics of tumors, and finish by outlining challenges and future directions of the field that may ultimately improve anti-cancer therapies.

Keywords: Drug transport in cancer; Engineering models of tumor; Tumor angiogenesis; Tumor desmoplasia; Tumor microenvironment.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Biological Transport / drug effects
  • Biological Transport / physiology
  • Drug Delivery Systems / methods*
  • Drug Delivery Systems / trends
  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Neovascularization, Pathologic / drug therapy*
  • Neovascularization, Pathologic / pathology
  • Tissue Engineering / methods*
  • Tissue Engineering / trends


  • Antineoplastic Agents