Radiopharmaceutical Therapy and Immunotherapy Combinations Utilizing Cancer Evolution and Computational Modeling in Metastatic Prostate Cancer.

This review highlights the critical role of evolutionary dynamics in metastatic prostate cancer treatment. It emphasizes that resistance arises through Darwinian selection, often driven by continuous maximum tolerated dose therapies. Evolution-informed strategies, such as adaptive therapy and exploiting collateral sensitivities, aim to delay resistance and prolong disease control by steering tumor evolution. Radiopharmaceutical therapy, especially when combined with immunotherapy, offers promising avenues for targeting disseminated tumors. Integrating mathematical models and computer simulations to understand tumor evolution can optimize personalized, adaptive treatment regimens, transforming resistance from a failure into an exploitable vulnerability, ultimately improving outcomes in advanced prostate cancer.