Intersection Between Local Anesthetics and Cancer Biology: What Now? Where Are We Going?

Local anesthetics (LAs), commonly  used for   regional and  general anesthesia, have gained attention in recent  years for their potential role during cancer curative surgery, as they may reduce cancer recurrence and progression. Studies in both laboratory and animal models have shown that LAs can inhibit tumor growth and cell proliferation, trigger apoptosis, and reduce metastasis by limiting cancer cell invasion and migration. In addition, LAs impact the tumor microenvironment by modulating inflammation, enhancing the immune response, blocking angiogenesis, and interfering with tumor innervation. The mechanisms behind these effects involve both voltage-gated sodium channel-dependent and independent pathways, such as AKT/mTOR, RAS/ERK, and SRC/STAT3, as well as regulating microRNAs, circular RNAs, and apoptosis-related proteins, among others. Furthermore, LAs may enhance the efficacy of chemotherapy and counteract chemoresistance. The aim of this review is to provide a comprehensive summary of the current literature on the various mechanisms through which LAs influence tumorigenesis, alter metastasis processes, modulate immune responses, and affect angiogenesis within the tumor microenvironment.