Local Anesthetics in Cancer: Mechanisms and Translational Perspectives

ABSTRACT Local anesthetics, such as lidocaine and ropivacaine, are fundamental to perioperative pain management. Beyond anesthesia, growing evidence indicates that local anesthetics may exert anticancer effects, potentially improving long‐term oncologic outcomes by modulating tumor cell behavior and the perioperative environment. Surgery itself could promote metastasis via inflammatory and immunosuppressive pathways. However, the specific role and full therapeutic potential of local anesthetics in countering these effects are not fully defined. This review systematically synthesizes current understanding of the direct and indirect antitumor mechanisms of local anesthetics. We detail their direct inhibition of cancer cell proliferation through the induction of apoptosis and cell cycle arrest. The review also analyzes their indirect effects on the tumor microenvironment, which include enhancing antitumor immunity, attenuating surgery‐induced stress and systemic inflammation, and inhibiting angiogenesis. We explore the potential synergy between local anesthetics and established cancer therapies, such as immunotherapy and targeted agents. Finally, the clinical evidence was appraised critically, discussing observational studies and the limited interventional trials linking regional anesthesia to improved survival, while addressing heterogeneity and confounding factors. By synthesizing mechanistic insights with clinical data, this review establishes a foundation for future research and highlights the translational potential of local anesthetics as adjuncts in perioperative cancer care.