Local anesthetics, regional anesthesia and cancer biology

Local anesthetics (LAs) have been widely used for over a century in perioperative care. Emerging evidence suggests that LAs impact on cancer cell biology through multiple mechanisms, including modulation of tumor cell proliferation, apoptosis, and metastasis, as well as in processes related to the tumor microenvironment such as angiogenesis and the immune response. These effects are attributed to LAs effect on membrane proteins, such as voltage gated sodium channels (VGSC) and caveolin-1, oncogenic pathways, such as PI3K/AKT/mTOR and RAS/MAPK/ERK axis, and gene transcription signaling regulation, including intermediates such as NF-κB and STAT3. Furthermore, LAs modulate cancer cells by promoting caspase activation and inducing oxidative stress, as well as regulating different organelle's function and structure. LAs role as adjuvant agents for stablished and experimental chemotherapeutic drugs have further been described in multiple in vitro experiments. In vivo models have also been used to demonstrate that LAs might be able to reduce tumor burden and metastasis in animals, highlighting their potential role in cancer treatment. However, despite promising preclinical findings, further research is needed to establish clinical relevance and optimize the use of LAs in oncological surgery. The aim of this review article is to summarize the currently available preclinical evidence of the effects of LAs and regional anesthesia on cancer spread.