Breast and prostate cancers, two of the most prevalent malignancies worldwide, pose sig-nificant therapeutic challenges due to resistance to conventional treatments and their complex tumor microenvironments. The integration of innovative therapies into current clinical frameworks is essential to improve patient outcomes. SN-38, the active metabolite of irinotecan, has emerged as a potent chemotherapeutic agent with broad anti-cancer ac-tivity, primarily through its inhibition of topoisomerase I, leading to irreparable DNA damage and apoptosis in cancer cells. Concurrently, immunotherapy has revolutionized oncology by harnessing the immune system to target and eliminate tumors, yet its effec-tiveness in hormone-driven cancers has been limited by immunosuppressive tumor mi-croenvironments and adaptive resistance mechanisms. This review explores the potential synergy between SN-38 and immunotherapy in the management of breast and prostate cancers. Evidence suggests that SN-38 not only exerts direct cytotoxic effects but also pro-motes immunogenic cell death, enhancing the efficacy of immune checkpoint inhibitors and other immunotherapeutic modalities. By modulating the tumor microenvironment and disrupting key DNA repair pathways, SN-38 may amplify the anti-tumor immune response, providing a dual mechanism for combating resistant and aggressive cancer phenotypes. Future directions emphasize the optimization of SN-38 formulations, such as nanoparticle delivery systems, to enhance bioavailability and minimize toxicity, as well as the identification of predictive biomarkers for personalized treatment approaches. This synergistic strategy offers a promising avenue for overcoming therapeutic resistance and improving outcomes in breast and prostate cancer patients. By combining the precision of immunotherapy with the potency of SN-38, this approach could redefine the therapeutic landscape for these challenging malignancies and inspire further innovation in oncology.
Adekiya et al. (Wed,) studied this question.