Impairing energy metabolism in solid tumors through agents targeting oncogenic signaling pathways

Biochem Pharmacol. 2018 May:151:114-125. doi: 10.1016/j.bcp.2018.03.006. Epub 2018 Mar 9.

Abstract

Cell metabolic reprogramming is one of the main hallmarks of cancer and many oncogenic pathways that drive the cancer-promoting signals also drive the altered metabolism. This review focuses on recent data on the use of oncogene-targeting agents as potential modulators of deregulated metabolism in different solid cancers. Many drugs, originally designed to inhibit a specific target, then have turned out to have different effects involving also cell metabolism, which may contribute to the mechanisms underlying the growth inhibitory activity of these drugs. Metabolic reprogramming may also represent a way by which cancer cells escape from the selective pressure of targeted drugs and become resistant. Here we discuss how targeting metabolism could emerge as a new effective strategy to overcome such resistance. Finally, accumulating evidence indicates that cancer metabolic rewiring may have profound effects on tumor-infiltrating immune cells. Modulating cancer metabolic pathways through oncogene-targeting agents may not only restore more favorable conditions for proper lymphocytes activation, but also increase the persistence of memory T cells, thereby improving the efficacy of immune-surveillance.

Keywords: Cancer; Immunity; Metabolism; Resistance; Target therapy.

Publication types

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

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Carcinogens / metabolism
  • Energy Metabolism / drug effects*
  • Energy Metabolism / genetics
  • Glutamine / metabolism
  • Glycolysis / drug effects
  • Humans
  • Lipid Metabolism / drug effects
  • Neoplasms / genetics
  • Neoplasms / immunology
  • Neoplasms / metabolism*
  • Signal Transduction / drug effects*

Substances

  • Antineoplastic Agents
  • Carcinogens
  • Glutamine