Nerve growth factor & TrkA as novel therapeutic targets in cancer

Biochim Biophys Acta. 2016 Aug;1866(1):37-50. doi: 10.1016/j.bbcan.2016.05.003. Epub 2016 Jun 2.

Abstract

In the past 20years, nerve growth factor (NGF) and its receptors TrkA & p75NTR were recognized to be overexpressed in the overwhelming majority of human solid cancers. Recent studies discovered the presence of overactive TrkA signaling due to TrkA rearrangements or TrkA fusion products in frequent cancers like colorectal cancer, thyroid cancer, or acute myeloid leukemia. Thus, targeting TrkA/NGF via selective small-molecule-inhibitors or antibodies has gained enormous attention in the drug discovery sector. Clinical studies on the anti-cancer impact of NGF-blocking antibodies are likely to be accelerated after the recent removal of clinical holds on these agents by regulatory authorities. Based on these current developments, the present review provides not only a broad overview of the biological effects of NGF-TrkA-p75NTR on cancer cells and their microenvironment, but also explains why NGF and its receptors are going to evoke major interest as promising therapeutic anti-cancer targets in the coming decade.

Keywords: Cancer; Gene fusion; Gene rearrangement; Growth; Microenvironment; Monoclonal antibodies; NGF; Nerves; Pain; Therapeutic target; TrkA; p75NTR.

Publication types

  • Review

MeSH terms

  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Nerve Growth Factor / antagonists & inhibitors
  • Nerve Growth Factor / genetics*
  • Nerve Tissue Proteins / antagonists & inhibitors
  • Nerve Tissue Proteins / genetics*
  • Receptor, trkA / antagonists & inhibitors
  • Receptor, trkA / genetics*
  • Receptors, Nerve Growth Factor / antagonists & inhibitors
  • Receptors, Nerve Growth Factor / genetics*
  • Signal Transduction / drug effects
  • Small Molecule Libraries / therapeutic use
  • Tumor Microenvironment / drug effects

Substances

  • NGFR protein, human
  • NTRK1 protein, human
  • Nerve Tissue Proteins
  • Receptors, Nerve Growth Factor
  • Small Molecule Libraries
  • Nerve Growth Factor
  • Receptor, trkA