Unraveling the Anti-Cancer Mechanisms of Antibiotics: Current Insights, Controversies, and Future Perspectives.

Cancer persists as a significant global health challenge, claiming millions of lives annually despite remarkable strides in therapeutic innovation. Challenges such as drug resistance, toxicity, and suboptimal efficacy underscore the need for novel treatment paradigms. In this context, the repurposing of antibiotics as anti-cancer agents has emerged as an attractive prospect for investigation. Diverse classes of antibiotics have exhibited promising anti-cancer properties in both in vitro and in vivo studies. These mechanisms include the induction of apoptosis and cell cycle arrest, generation of reactive oxygen species, and inhibition of key regulators of cell proliferation and migration. Additional effects involve the disruption of angiogenesis and modulation of pivotal processes such as inflammation, immune response, mitochondrial dynamics, ferroptosis, and autophagy. Furthermore, antibiotics have demonstrated the potential to enhance the efficacy of conventional modalities like chemotherapy and radiotherapy, while alleviating treatment-induced toxicities. Nevertheless, the integration of antibiotics into oncological applications remains contentious, with concerns centered on their disruption of gut microbiota, interference with immunotherapeutic strategies, contribution to microbial resistance, and potential association with tumorigenesis. This narrative review explores the mechanisms of antibiotics' anti-cancer activity, addresses controversies about their dual role in cancer biology, and envisions future perspectives that include the development of novel derivatives and innovative frameworks for their incorporation into cancer treatment paradigms.