A multi-targeted approach to suppress tumor-promoting inflammation

Semin Cancer Biol. 2015 Dec:35 Suppl:S151-S184. doi: 10.1016/j.semcancer.2015.03.006. Epub 2015 May 5.

Abstract

Cancers harbor significant genetic heterogeneity and patterns of relapse following many therapies are due to evolved resistance to treatment. While efforts have been made to combine targeted therapies, significant levels of toxicity have stymied efforts to effectively treat cancer with multi-drug combinations using currently approved therapeutics. We discuss the relationship between tumor-promoting inflammation and cancer as part of a larger effort to develop a broad-spectrum therapeutic approach aimed at a wide range of targets to address this heterogeneity. Specifically, macrophage migration inhibitory factor, cyclooxygenase-2, transcription factor nuclear factor-κB, tumor necrosis factor alpha, inducible nitric oxide synthase, protein kinase B, and CXC chemokines are reviewed as important antiinflammatory targets while curcumin, resveratrol, epigallocatechin gallate, genistein, lycopene, and anthocyanins are reviewed as low-cost, low toxicity means by which these targets might all be reached simultaneously. Future translational work will need to assess the resulting synergies of rationally designed antiinflammatory mixtures (employing low-toxicity constituents), and then combine this with similar approaches targeting the most important pathways across the range of cancer hallmark phenotypes.

Keywords: Cancer; Hallmarks; Inflammation; Phytochemicals; Tumor.

Publication types

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

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Cell Transformation, Neoplastic / drug effects
  • Genetic Heterogeneity / drug effects
  • Humans
  • Inflammation / drug therapy*
  • Inflammation / genetics
  • Inflammation / pathology
  • Molecular Targeted Therapy
  • Neoplasm Proteins / antagonists & inhibitors*
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Neoplasms / pathology
  • Signal Transduction / drug effects

Substances

  • Antineoplastic Agents
  • Neoplasm Proteins