Mechanisms of Action by Which Local Anesthetics Reduce Cancer Recurrence: A Systematic Review

Abstract

BACKGROUND: Surgery in concert with anesthesia is a key part of the management of advanced-stage cancers. Anesthetic agents such as opioids and volatile anesthetics have been shown to promote recurrence in preclinical models, whereas some animal models have shown that the use of lidocaine may be beneficial in reducing cancer recurrence. The purpose of this article is to review the current literature to highlight the mechanisms of action by which local anesthetics are thought to reduce cancer recurrence. METHODS: A systematic review was conducted using the PubMed (1966 to 2018) electronic database. Search terms included "lidocaine," "ropivicaine," "procaine," "bupivicaine," "mepivicaine," "metastasis," "cancer recurrence," "angiogenesis," and "local anesthetics" in various combinations. The search yielded 146 total abstracts for initial review, 20 of which met criteria for inclusion. Theories for lidocaine's effect on cancer recurrence were recorded. All studies were reviewed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. RESULTS: Numerous mechanisms were proposed based on the local anesthetic used and the type of cancer. Mechanisms include those that are centered on endothelial growth factor receptor, voltage-gated sodium and calcium channels, transient receptor melanoplastin 7, hyperthermia, cell cycle, and demyelination. CONCLUSIONS: In vivo models suggest that local anesthetic administration leads to reduced cancer recurrence. The etiology of this effect is likely multifactorial through both inhibition of certain pathways and direct induction of apoptosis, a decrease in tumor migration, and an association with cell cycle-mediated and DNA-mediated effects. Additional research is required to further define the clinical implications.