Combining Chemotherapeutic Agents, Targeted Therapies, Vaccines and Natural Bioactive Compounds for Mesothelioma: Advances and Perspectives.

Mesothelioma is a rare and aggressive cancer with a poor prognosis and limited therapeutic options. Despite recent advances, conventional treatment approaches remain largely ineffective due to late diagnosis, chemoresistance and immunosuppressive tumor microenvironment. This review reports the latest studies on combination therapies for mesothelioma, focusing on the potential of integrating chemotherapeutic agents, molecularly targeted agents, vaccines and natural bioactive compounds such as polyphenols. Clinical and preclinical studies demonstrate that integrating immune-modulating drugs or molecular inhibitors with chemotherapy can improve survival and reduce tumor progression in mesothelioma models and patients. Vaccine-based strategies show potential for inducing host-persistent immune responses when combined with conventional treatments. Moreover, natural compounds such as polyphenols show synergistic effects with chemotherapeutics and targeted agents by modulating several signaling pathways involved in cancer cell growth and progression and by overcoming drug resistance. While several combination strategies are under clinical investigation, further studies are needed to develop more effective and personalized therapeutic approaches that could be translated into standardized treatment protocols.