Neurotrophic Tyrosine Kinase Gene Fusions: Another Opportunity for Targeting in Lung Cancer

Abstract

Neurotrophic tyrosine kinase gene fusions Neurotrophic tyrosine kinase (NTRK) genes encode for the Trk-family proteins: TrkA (encoded by NTRK1), TrkB (encoded by NTRK2) and TrkC (encoded by NTRK3). These family proteins normally play a role in the development of the CNS and PNS [1]. They modulate cells growth, proliferation, repair, maintenance and apoptosis [2]. Lately, NTRK fusions have been found in solid tumors creating oncogenic fusions responsible for transformation of cancer cells, proliferation and survival [3]. Several studies have documented how the presence of these three gene fusions is associate with worse survivals in all types of lung cancers [4]. NTRK1 oncogenic fusions have been detected by FISH or next-generation sequencing (NGS) in about 3% of NSCLC, while NTRK2 and NTRK3 fusions in about 1% of NSCLC including all types [3,5]. However, there are other two studies that found very low numbers in patients with early stage NSCLC after tumor resection [6,7]. Also, we emphasize the presence of the fusion gene for its oncogenic potential because other alterations like point mutations can be found in these genes with no relevant oncogenic potential [5].