The neuronal network of small cell lung cancer: a narrative review of the role of the nervous system in the pathogenesis and progression

Background and Objective: Small cell lung cancer (SCLC) is a highly aggressive cancer with a poor prognosis, in which increasing attention is focused on the role of the nervous system as an active regulator of cancer initiation, progression and metastasis. The aim of this study is to provide an integrated focus on SCLC review of the mechanisms of neuronal regulation of this cancer, as well as a critical analysis of their therapeutic potential.

Methods: A literature review was conducted in the PubMed database, covering publications from 1st January 2020 to 1st December 2025, using defined keywords relating to SCLC and the nervous system. The analysis included publications that met the criteria relating to the role of the nervous system in the pathogenesis, progression or treatment of SCLC.

Key Content and Findings: The review identifies the multi-level influence of the nervous system on SCLC, including: the formation of functional synapses between cancer cells and neurons, the relevance of vagotomy in the early stages of carcinogenesis, the role of neurotransmitters and their receptors, neuropeptides and neurotrophins in tumour development and their influence on the tumour microenvironment, as well as the interaction of SCLC with astrocytes in brain metastases (including Reelin and SERPINE1). Therapeutic perspectives were also discussed, including the use of ADRB2 blockade, the inhibition of synaptic neurotransmission, and the blockade of the neurotrophin axis.

Conclusions: The findings presented in this study provide a basis for further research into the interactions between SCLC and the nervous system, with a view to developing new targeted treatments in the future.