Neural-cancer Crosstalk: Reciprocal Molecular Circuits Driving Gastric Tumorigenesis and Emerging Therapeutic Opportunities.

Abstract

The nervous system plays an important role in regulating physiological functions of the stomach, and its abnormal activity often impairs gastric homeostasis. In response to constant exposure to oncogenic stimuli that leads to gastric tumorigenesis, the neural system becomes an essential component of the tumor microenvironment via perineural infiltration, de novo neurogenesis, and axonogenesis, thereby driving cancer initiation and progression. In this review, we highlight emerging discoveries related to neural-cancer crosstalk and discuss how the nervous system is remodeled by tumor cells including neural components and modulators (including neurotransmitters and neuropeptides). Moreover, we provide a systematic analysis of neural control of the cellular hallmarks of cancer. Finally, we propose how the molecular circuits of neural-cancer crosstalk could be exploited as potential targets for novel anti-cancer treatment, providing new insights into a new modality of neural-based cancer therapeutic strategies.