Metastatic Castration Resistant Prostate Cancer

Novel Ways of Targeting the Androgen Receptor

by Daniel P. Petrylak, MD | Sep 2024

Daniel P. Petrylak, MD, explores novel approaches for targeting the androgen receptor (AR) in prostate cancer, highlighting that around 90% of prostate cancer specimens express the androgen receptor, which persists through castrate resistance.

In this 7-minute talk, Dr. Petrylak focuses on targeting the AR ligand-binding domain with molecules known as proteolysis-targeting chimeras (PROTACs). Laboratory findings reveal that PROTACs can degrade AR variants resistant to traditional therapies like enzalutamide, showing efficacy against androgen gene amplification mutations.

He shares that ARV-110, a PROTAC developed for clinical use, showed promise in phase 1 trials with castration-resistant prostate cancer patients. However, due to significant side effects, the ARV-110 trials were abandoned in favor of a newer compound, ARV-766. While ARV-110 has demonstrated efficacy in castration-resistant prostate cancer, ARV-766 offers a broader range of AR degradation with improved patient tolerance, making it the preferred candidate for continued clinical evaluation.

PARPi in mCRPC

by Daniel P. Petrylak, MD | Sep 2024

Daniel P. Petrylak, MD, Yale University Cancer Center, New Haven, Connecticut, summarizes the current and future role of PARP inhibitors in mCRPC, providing valuable insights into their clinical application and potential to improve patient outcomes.

In this 9-minute presentation, Dr. Henderson highlights direct costs such as medications, hospital stays, and physician fees, as well as indirect costs including lost income and travel expenses. He emphasizes that these financial strains can lead to treatment non-adherence, delayed care, and worsened clinical outcomes.

Dr. Henderson discusses various strategies and interventions to address these challenges, underscoring the importance of policy changes at the institutional and governmental levels to improve access to affordable care.

Understanding Metastatic Castration-Resistant Prostate Cancer

by Shell Liang, PhD | Jun 2024

Shell Liang, PhD, discusses metastatic castration-resistant prostate cancer (mCRPC), a form of prostate cancer that progresses despite androgen deprivation therapy (ADT). Dr. Liang emphasizes the critical need for advanced therapeutic strategies to manage this aggressive cancer subtype effectively.
The presentation reviews the current therapeutic landscape for mCRPC, focusing on second-generation AR pathway inhibitors such as abiraterone and enzalutamide. Additionally, the discussion includes the role of chemotherapeutic agents like docetaxel and cabazitaxel. Dr. Liang also explores emerging treatment modalities, including PARP inhibitors and immunotherapies.
Dr. Liang advocates using genomic profiling to identify actionable mutations and tailor treatments to individual patient profiles. This approach aims to optimize therapeutic efficacy and minimize adverse effects, aligning with the principles of precision medicine.

Metastatic Castrate-Resistant Prostate Cancer: Options and Possible Sequences

by A. Oliver Sartor, MD | Nov 2023

Dr. A. Oliver Sartor outlines the available therapeutic options for metastatic castrate-resistant prostate cancer (mCRPC), which include novel hormonal agents, chemotherapy, immunotherapy, and targeted therapies. He addresses androgen receptor signaling inhibitors such as abiraterone acetate and enzalutamide, and the use of chemotherapy agents like docetaxel and cabazitaxel.

Dr. Sartor also addresses the emerging role of immunotherapy in mCRPC, particularly with agents like pembrolizumab for patients with specific genetic mutations or microsatellite instability. Additionally, he discusses the potential of radionuclide therapies, such as radium-223.

mCRPC – Inroads in Improved Outcomes

by Daniel P. Petrylak, MD | Apr 2023

Daniel P. Petrylak, MD, discusses inroads to improved outcomes in the treatment of metastatic castration-resistant prostate cancer (mCRPC).

PCa Commentary | Volume 176 – April 2023

by Edward Weber, MD | Apr 2023

This Commentary reviews the underlying biology of PARP inhibitors and data supporting olaparib plus abiraterone as first-line therapy for mCRPC.

NCCN Guidelines for Treatment of Localized Prostate Cancer

by Kelvin A. Moses, MD, PhD, FACS | Apr 2023

Kelvin A. Moses, MD, PhD, FACS, discusses updates to the National Comprehensive Cancer Network (NCCN) guidelines for localized prostate cancer treatment.

PCa Commentary | Volume 173 – January 2023

by Edward Weber, MD | Jan 2023

This Commentary discusses Bipolar Androgen Therapy: an effective, but likely underused, option in the sequence of treatments for mCRPC.

PCa Commentary | Volume 172 – December 2022

by Edward Weber, MD | Dec 2022

This Commentary discusses selecting men for MDT+ADT versus MDT alone in the oligometastatic prostate cancer space.

New Standards of Care for Advanced Prostate Cancer

by William K. Oh, MD | Dec 2022

In this 20-minute presentation, William K. Oh, MD, Chief of the Division of Hematology and Medical Oncology at the Mount Sinai Health System and Deputy Director of The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai, addresses new standards of care in 2021 for advanced prostate cancer and focuses on non-metastatic castration-resistant prostate cancer (nmCRPC), concluding that apalutamide, enzalutamide, and darolutamide improve MFS in men with nmCRPC by ~2 years; SPARTAN, PROSPER, and ARAMIS established favorable benefit-risk for patients with nmCRPC and PSADT<10 months; and these studies provide the best evidence supporting early treatment. He also focuses on metastatic, hormone-sensitive prostate cancer (mHSPC) and concludes that upfront treatment with either abiraterone + prednisone, apalutamide, enzalutamide, or docetaxel is the standard of care and he asserts that new evidence from PEACE-1 and ARASENS supports triple therapy with a novel hormonal therapy +ADT+docetaxel for chemotherapy patients.