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Related Experiment Video

Updated: May 9, 2025

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
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Advances in Targeted Therapy for Metastatic Prostate Cancer.

Kabir Grewal1, Tanya B Dorff2, Sagar S Mukhida3

  • 1Department of Internal Medicine, Baylor College of Medicine, Houston, TX, USA.

Current Treatment Options in Oncology
|April 29, 2025
PubMed
Summary

Biomarker-driven treatments are revolutionizing advanced prostate cancer care. Poly-ADP-ribose-polymerase (PARP) inhibitors and androgen receptor (AR) pathway inhibitors offer new hope, especially for patients with specific mutations.

Keywords:
ARCell surface proteinDNA damage repairPARP inhibitorPROTACPSMASTEAP- 1

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Area of Science:

  • Oncology
  • Genetics
  • Pharmacology

Background:

  • Advanced prostate cancer treatment is evolving from a uniform approach to personalized, biomarker-guided therapies.
  • Key areas of advancement include poly-ADP-ribose-polymerase (PARP) inhibitors, novel androgen receptor (AR) targeting strategies, and cell surface protein-directed therapies.

Purpose of the Study:

  • To review current and emerging therapeutic strategies for metastatic prostate cancer.
  • To highlight the role of PARP inhibitors, AR pathway inhibitors, and cell surface protein-targeting agents.

Main Methods:

  • Review of current literature and clinical trial data on advanced prostate cancer treatments.
  • Discussion of specific therapeutic classes: PARP inhibitors, AR pathway inhibitors, radioligand therapies, bispecific T cell engagers, and antibody-drug conjugates.

Main Results:

  • Combination therapy with PARP inhibitors (PARPi) and AR pathway inhibitors (ARPI) is favored for homologous recombination repair (HRR)-mutated metastatic castration-resistant prostate cancer (CRPC) patients who can tolerate it.
  • PARPi monotherapy benefits patients with BRCA1 or BRCA2 mutations unable to tolerate combination treatment.
  • New AR-directed therapies (ligand degraders, CYP11A1 inhibitors) show promise for metastatic CRPC, potentially benefiting earlier disease stages.
  • Radioligand therapy (177Lu-PSMA-617) is effective for PSMA-avid metastatic CRPC post-ARPI and chemotherapy.
  • Bispecific T-cell engagers and novel radioligand therapies targeting cell surface proteins show promising survival benefits.

Conclusions:

  • Personalized medicine, utilizing biomarker-based therapies, is transforming advanced prostate cancer management.
  • PARP inhibitors and AR-directed therapies represent significant progress, with combination strategies and monotherapy offering tailored options.
  • Targeting cell surface proteins via radioligand therapy and bispecific T-cell engagers presents a promising frontier for improving patient survival.