PARP Inhibitors and Radiometabolic Approaches in Metastatic Castration-Resistant Prostate Cancer: What’s Now, What’s New, and What’s Coming?

SIMPLE SUMMARY: Prostate cancer still represents an important health problem in men, considering its high frequency. Over the last decade, novel treatment options have emerged, leading to notable clinical benefits. These recent scientific acquisitions are creating the basis to widen the treatment scenario of this tumor, evolving from targeting the androgen receptor axis or the traditional chemotherapy approach. ABSTRACT: In recent years, the advances in the knowledge on the molecular characteristics of prostate cancer is allowing to explore novel treatment scenarios. Furthermore, technological discoveries are widening diagnostic and treatment weapons at the clinician disposal. Among these, great relevance is being gained by PARP inhibitors and radiometabolic approaches. The result is that DNA repair genes need to be altered in a high percentage of patients with metastatic prostate cancer, making these patients optimal candidates for PARP inhibitors. These compounds have already been proved to be active in pretreated patients and are currently being investigated in other settings. Radiometabolic approaches combine specific prostate cancer cell ligands to radioactive particles, thus allowing to deliver cytotoxic radiations in cancer cells. Among these, radium-223 and lutetium-177 have shown promising activity in metastatic pretreated prostate cancer patients and further studies are ongoing to expand the applications of this therapeutic approach. In addition, nuclear medicine techniques also have an important diagnostic role in prostate cancer. Herein, we report the state of the art on the knowledge on PARP inhibitors and radiometabolic approaches in advanced prostate cancer and present ongoing clinical trials that will hopefully expand these two treatment fields.