Nerve growth factor & TrkA as novel therapeutic targets in cancer.
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.
Department of Surgery, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany. Electronic address: ekin.demir@tum.de.
Ihsan Ekin
IE
Demir
Department of Surgery, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany.
Elke
E
Tieftrunk
Department of Surgery, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany.
Stephan
S
Schorn
Department of Surgery, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany.
Helmut
H
Friess
Department of Surgery, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany.
Güralp O
GO
Ceyhan
D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics; D020932:Nerve Growth Factor / Q000037:antagonists & inhibitors / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000235:genetics*; D020917:Receptor, trkA / Q000037:antagonists & inhibitors / Q000235:genetics*; D017475:Receptors, Nerve Growth Factor / Q000037:antagonists & inhibitors / Q000235:genetics*; D015398:Signal Transduction / Q000187:drug effects; D054852:Small Molecule Libraries / Q000627:therapeutic use; D059016:Tumor Microenvironment / Q000187:drug effects
C484065:NGFR protein, human; C000611485:NTRK1 protein, human; D009419:Nerve Tissue Proteins; D017475:Receptors, Nerve Growth Factor; D054852:Small Molecule Libraries; D020932:Nerve Growth Factor; D020917:Receptor, trkA
Cancer; Gene fusion; Gene rearrangement; Growth; Microenvironment; Monoclonal antibodies; NGF; Nerves; Pain; Therapeutic target; TrkA; p75NTR