DURHAM, NC — Novel therapies are being investigated for metastatic castration resistant prostate cancer, according to a new review.

The report in Prostate Cancer and Prostatic Diseases noted that androgen-targeted therapy and chemotherapy are the current standard treatment for mCRPC and that, when progression occurs despite those therapeutic strategies, no additional Food and Drug Administration-approved treatment options are available.1

That might be changing, however, according to authors from the Duke University School of Medicine and the Durham, NC, VA Healthcare System.

To put a spotlight on emerging data surrounding novel investigational therapies, the team reviewed and summarized the body of literature surrounding current treatment options for mCRPC. They gathered information from Medline and Pubmed as well as abstracts from international congresses to find relevant literature on investigational treatments for mCRPC.

“Androgen-targeted therapy and chemotherapy will remain foundational in the treatment of mCRPC,” the reviewers wrote. “However, heavily pretreated patients who have developed resistance may benefit from novel therapeutic strategies. The use of poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitors (PARPi) has now gained FDA approval for patients with homologous recombination repair (HRR) gene mutations. Novel androgen receptor (AR) degraders and the use of radioligand therapy (RLT) with Lu-PSMA-617 (Lu-PSMA) are under investigation. Immune-directed therapies, including programmed death (PD-1) inhibition, bi-specific T-cell engager (BiTE) technology, and chimeric antigen receptor (CAR) T-cell therapy, have shown promise in early phase trials. Further understanding of resistance mechanisms has led to additional therapeutic targets, including targeting the PI3K-Akt-mTOR pathway and enhancer of zester homolog 2 (EZH2).”

Emphasizing that additional data from randomized trials will be necessary to determine efficacy and tolerability of novel treatment strategies, the authors concluded, “Based on our review of the literature, exciting new therapeutic strategies exist for the treatment of mCRPC. In particular, PARPi, AR degraders, PSMA-targeted therapies, immune-directed therapies, and agents targeting resistance mechanisms as monotherapy or in combination could improve patient outcomes.”


  1. Labriola MK, Atiq S, Hirshman N, Bitting RL. Management of men with metastatic castration-resistant prostate cancer following potent androgen receptor inhibition: a review of novel investigational therapies. Prostate Cancer Prostatic Dis. 2020 Nov 9. doi: 10.1038/s41391-020-00299-9. Epub ahead of print. PMID: 33168966.