The mesenchymal tumor microenvironment: a drug-resistant niche

Cell Adh Migr. May-Jun 2012;6(3):285-96. doi: 10.4161/cam.20210. Epub 2012 May 1.

Abstract

Drug and radiation resistance represent a challenge for most anticancer therapies. Diverse experimental approaches have provided evidence that the tumor-associated microenvironment constitutes both a protective shell that impedes drug or radiation access and a permissive or promotive microenvironment that encourages a nurturing cancer (i.e., cancer stem cell) niche where tumor cells overcome treatment- and cancer-induced stresses. Better understanding of the effects of the tumor microenvironment on cancer cells before, during and immediately after chemo- or radiotherapy is imperative to design new therapies aimed at targeting this tumor-protective niche. This review summarizes some of the known mesenchymal stromal effects that account for drug resistance, the main signal transduction pathways associated with this resistance and the therapeutic efforts directed to increase the success of current therapies. Special emphasis is given to environment-mediated drug resistance in general and to cell adhesion-mediated drug resistance in particular.

Publication types

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

MeSH terms

  • Animals
  • Cell Adhesion
  • Drug Resistance, Neoplasm*
  • Humans
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Mesoderm / pathology*
  • Neoplasms / drug therapy*
  • Neoplasms / mortality
  • Neoplasms / pathology
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology
  • Neoplastic Stem Cells / physiology
  • Paracrine Communication
  • Signal Transduction
  • Stromal Cells / metabolism
  • Stromal Cells / pathology
  • Stromal Cells / physiology
  • Tumor Microenvironment / drug effects*

Substances

  • Intercellular Signaling Peptides and Proteins