Oncogenic influences of neurotrophin receptors: Shedding light on Trk biology

During critical stages of neurodevelopment, tropomyosin receptor kinase receptors, encoded by NTRK genes, exhibit temporally driven differential peaks of expression to properly guide the establishment of the peripheral and central nervous systems. In addition, these neuronal systems exhibit non-canonical regulation of surrounding tissues, impacting organogenesis, homeostasis, plasticity, and regeneration. The same processes that guide neurodevelopment, such as differentiation, plasticity, and neuronal survival, are also hijacked in cancer, making the NTRK family an ideal candidate to study. The Trk receptor family plays a critical role in both normal development and several cancer hallmark pathways such as anti-apoptotic signaling, abnormal cellular proliferation, metastasis, and stemness. It is paramount to understand the molecular underpinnings that Trk receptors play in driving malignancy and the specificity of current therapeutics. This review explores key implications of the NTRK gene family in the pathophysiological mechanisms driving cancers within and outside the central nervous system.