Increased sympathetic nervous system impairs prognosis in lung cancer patients: a scoping review of clinical studies

Aim: To summarize current knowledge, gaps, quality of the evidence and show main results related to the role of the autonomic nervous system in lung cancer. Methods: Studies were identified through electronic databases (PubMed, Scopus, Embase and Cochrane Library) in October 2023, and a descriptive analysis was performed. Twenty-four studies were included, and most were observational. Results: Our data indicated an increased expression of beta-2-adrenergic receptors in lung cancer, which was associated with poor prognosis. However, the use of beta-blockers as an add-on to standard treatment promoted enhanced overall survival, recurrence-free survival and reduced metastasis occurrence. Conclusion: Although the results herein seem promising, future research using high-quality prospective clinical trials is required to draw directions to guide clinical interventions. Lung cancer is one of the most common causes of cancer-related deaths in the world, which often goes undiagnosed until it is in an advanced stage. Recently, the autonomic nervous system (sympathetic and parasympathetic nervous systems) has been identified as a regulator of cancer growth and spread, including lung cancer. In fact, preclinical studies have demonstrated that autonomic innervation in lung cancer can trigger tumor progression, metastasis, and resistance to treatment, worsening the prognosis. In this sense, add-on strategies to standard cancer treatments have been investigating and one of them has stood out: the incidental use of beta-blockers (patients who used beta-blockers for the treatment of hypertension and/or cardiovascular diseases or anxiety) before surgeries or during chemotherapy, which has been associated with improved clinical outcomes. Thus, a scoping review was conducted to summarizing the current knowledge about the quality of evidence, gaps and main results related to the role of the autonomic nervous system in human lung cancer. Data from this review indicated an increase in sympathetic nervous system receptors associated with a worse prognosis in patients with lung cancer. Indeed, those patients who took beta-blockers along with lung cancer treatment showed an increase in survival and a reduction in the occurrence of metastases. Although the results herein seem promising, further prospective clinical studies are needed to investigate the effect of the intentional and controlled use of beta-blockers as an add-on strategy on the treatment of different types and stages of lung cancer. An increased expression of beta-2-adrenergic receptors is linked to a poor prognosis in lung cancer. Adding beta-blockers to treatment improved survival and reduced metastasis. See more in our study.