Genetic and epigenetic cancer chemoprevention on molecular targets during multistage carcinogenesis

Arch Toxicol. 2016 Oct;90(10):2389-404. doi: 10.1007/s00204-016-1813-9. Epub 2016 Aug 19.

Abstract

The main goal of cancer chemoprevention is to prevent or halt the progression of carcinogenesis with the administration of synthetic or natural compounds. Fundamental chemopreventive strategies include inhibition of genetic damage, anti-proliferation/cell cycle regulation, and induction of apoptosis and anti-inflammatory processes, which may be critical for carcinogenesis intervention. Recently, a new paradigm for identifying chemopreventive agents has been implemented. It focuses on defining new biomarkers that can be used to evaluate chemopreventive efficacy based on multistage carcinogenesis. The functional roles of chemopreventive agents are associated with the modulation of nuclear factor kappa B, nuclear factor erythroid 2-related factor, p53, AMPK/mTOR, phosphatidylinositol 3-kinase, epidermal growth factor receptor, cyclooxygenase-2, chemokine (C-X-C motif) receptor 2, and sphingosine-1-phosphate. This paper summarizes the genetic and epigenetic effects of chemopreventive agents on the expression of cancer-related target genes mediated by epigenetic alterations, such as DNA methylation and histone modifications. This review will provide unique and effective strategies for reducing cancer and aging-related diseases in humans.

Keywords: Biomarkers; Chemoprevention; Epigenetic; Genetic; Inflammation; Multistage.

Publication types

  • Review

MeSH terms

  • Anticarcinogenic Agents / administration & dosage
  • Anticarcinogenic Agents / pharmacology
  • Anticarcinogenic Agents / therapeutic use*
  • Biomarkers, Tumor / genetics*
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • Chemoprevention
  • Clinical Trials as Topic
  • DNA Methylation / drug effects
  • Epigenesis, Genetic / drug effects*
  • Humans
  • Molecular Targeted Therapy / methods*
  • Neoplasm Staging
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Neoplasms / prevention & control*

Substances

  • Anticarcinogenic Agents
  • Biomarkers, Tumor