Leveraging Synergy: A Review of the Therapeutic Potential of SN-38 and Immune Checkpoint Blockade in Breast and Prostate Cancer Treatment

Breast and prostate cancers, two of the most prevalent malignancies worldwide, pose significant therapeutic challenges owing to their resistance to conventional treatments and complex tumor microenvironments. The integration of innovative therapies into current clinical frameworks is essential for improving patient outcomes. SN-38, an active metabolite of irinotecan, exerts potent antitumor effects by inhibiting topoisomerase I and modulating the tumor microenvironment. In addition to direct cytotoxicity, SN-38 induces immunogenic cell death, promotes damage-associated molecular pattern (DAMP) release, and enhances antitumor immune responses. These dual mechanisms support the potential of combining it with chemotherapy, targeted therapy, and immunotherapy, particularly in breast and prostate cancers. However, challenges such as poor solubility, rapid degradation, and dose-limiting toxicity hinder its clinical translation. Novel delivery systems, including liposomal formulations, antibody–drug conjugates, and nanoparticle-based strategies, are being developed to address these limitations. This review summarizes the current evidence on SN-38 alone and in combination with emerging therapies, highlighting its potential as a dual cytotoxic and immune-modulating agent in resistant and aggressive cancers.