Targeting Inflammation to Improve Tumor Drug Delivery

Trends Cancer. 2017 Sep;3(9):621-630. doi: 10.1016/j.trecan.2017.07.006. Epub 2017 Aug 23.

Abstract

Inefficient delivery of drugs is a main cause of chemotherapy failure in hypoperfused tumors. To enhance perfusion and drug delivery in these tumors, two strategies have been developed: vascular normalization, aiming at normalizing tumor vasculature and blood vessel leakiness, and stress alleviation, aiming at decompressing tumor vessels. Vascular normalization is based on anti-angiogenic drugs, whereas stress alleviation is based on stroma-depleting agents. We present here an alternative approach to normalize tumor vasculature, taking into account that malignant tumors tend to develop at sites of chronic inflammation. Similarly to tumor vessel leakiness, inflammation is also characterized by vascular hyperpermeability. Therefore, testing the ability of anti-inflammatory agents, such as non-steroidal anti-inflammatory drugs (NSAIDs) or inflammation resolution mediators, as an alternative means to increase tumor drug delivery might prove promising.

Keywords: anti-inflammatory agents; inflammation resolution; stress alleviation; tumor perfusion; vascular normalization.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacokinetics
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / therapeutic use*
  • Cancer-Associated Fibroblasts / drug effects
  • Cancer-Associated Fibroblasts / metabolism
  • Cancer-Associated Fibroblasts / pathology
  • Capillary Permeability
  • Extracellular Matrix
  • Humans
  • Inflammation / complications
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Inflammation / pathology*
  • Inflammation Mediators / metabolism
  • Neoplasms / drug therapy*
  • Neoplasms / etiology
  • Neoplasms / metabolism
  • Neoplasms / pathology*
  • Neovascularization, Pathologic / drug therapy
  • Neovascularization, Pathologic / metabolism
  • Tissue Distribution
  • Treatment Outcome
  • Tumor Microenvironment / drug effects

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Antineoplastic Agents
  • Inflammation Mediators