The peripheral tumor neuro-microenvironment: Deciphering neural landscape and mechanistic insights for therapeutic innovation.

As the nascent field of cancer neuroscience experiences explosive growth, the critical importance of the peripheral nervous system (PNS) in the onset, progression, and therapeutic approaches of cancer has garnered considerable attention from researchers in recent years. The neural-tumor interactions mediated by PNS components in the tumor microenvironment (TME) constitute the neural landscape of peripheral cancers, where neural activity regulates metastatic competence through structural innervation networks, neurochemical signaling cascades, and immune microenvironment remodeling. Within the TME, the synergistic interplay among cancer cells, neurons, and schwann cells establishes a dynamic neural ecological niche that orchestrates both oncogenic expansion and aberrant neural reorganization. This reflects an innovative theoretical framework of microenvironment-driven neural plasticity in cancer pathogenesis. We pioneer the conceptualization of "tumor neuro-microenvironment (TNME)", elucidating the pivotal roles of the PNS in orchestrating TNME dynamics via intricate neural-tumor interactions. By deeply dissecting the interactive networks between the PNS and TNME, as well as their mechanistic insights, we articulate the latest advancements in targeted PNS interventions for cancer therapy. This showcases its tremendous potential in anti-cancer efforts, paving the way for novel perspectives and therapeutic approaches in neuroscience-oriented cancer treatment strategies.