mCRPC VL

Opevesostat Trial in mCRPC: Targeting Androgen Biosynthesis Upstream for Improved Outcomes - Christian Gratzke

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Christian Gratzke discusses the Phase III trial of opevesostat, a CYP11A1 inhibitor, for metastatic castration-resistant prostate cancer (mCRPC). The study examines opevesostat's unique mechanism of targeting androgen biosynthesis upstream of current treatments, potentially offering more complete testosterone suppression than existing therapies. The ongoing 1,500-patient trial compares opevesostat...

ProstACT GLOBAL Trial: Combining PSMA-Targeted Therapy with ARPIs and Docetaxel - Oliver Sartor

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Oliver Sartor discusses the ProstACT GLOBAL trial design, examining TLX591, a PSMA-targeting antibody bound to lutetium-177 for metastatic castration-resistant prostate cancer treatment. The phase III trial includes a 30-patient safety lead-in followed by a 400-patient randomized study comparing standard of care (ARPI switch or docetaxel) with or without TLX591. Unlike other PSMA-targeted therapie...

Combining EZH2 and AR Targeting in Metastatic Castration-Resistant Prostate Cancer - Neeraj Agarwal

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Zachary Klaassen speaks with Neeraj Agarwal about the Phase III randomized MEVPRO-1 study examining mevrometostat in combination with enzalutamide for mCRPC patients previously treated with abiraterone acetate. Dr. Agarwal explains that EZH2, a key component of the Polycomb Repressive Complex II, functions by adding methyl groups to histone proteins, leading to gene silencing. The trial randomizes...

AR Enhancer Amplification and SSTR1 Downregulation in mCRPC - Xiaolin Zhu

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Andrea Miyahira interviews Xiaolin Zhu about a publication examining genomic and transcriptomic features of androgen receptor signaling inhibitor (ARSI) resistance in metastatic castration-resistant prostate cancer. Through analysis of paired metastatic biopsies taken before ARSI treatment and at disease progression, Dr. Zhu's team identifies three significant findings: a novel amplified enhancer...

Effectiveness of PSMA-Lutetium for Prostate Cancer Liver Metastases - Daniel Childs

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Daniel Childs discusses real-world outcomes of lutetium-PSMA-617 treatment in prostate cancer patients with liver metastases, based on Mayo Clinic registry data. Dr. Childs presents findings showing that patients with liver metastases experience shorter overall survival (approximately 8.3 months), complete fewer treatment cycles, and demonstrate lower PSA response rates compared to those without l...

Tumor Dosimetry in PSMA Therapy: A VISION Substudy Analysis - Ken Herrmann

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Oliver Sartor host Ken Herrmann to discuss tumor dosimetry findings from a VISION trial substudy examining lutetium PSMA therapy in prostate cancer patients. Dr. Herrmann presents data showing that tumor-absorbed dose per injected activity decreases significantly across treatment cycles, with approximately 60% of cumulative absorbed dose occurring in the first two cycles. He explores differences i...

Coagulation Factor X Promotes Resistance to Androgen-Deprivation Therapy in Prostate Cancer - Bianca Calì

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Andrea Miyahira interviews Bianca Cali about a Cancer Cell paper examining the role of Coagulation Factor X in prostate cancer treatment resistance. Dr. Cali discusses their discovery that polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) in tumors produce Factor X (F10), which promotes androgen-independent cell proliferation through PAR2 receptor signaling. The research identifies a...

RaLu Trial: Sequence of Radium Then Lutetium in mCRPC Management - Kambiz Rahbar

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Oliver Sartor and Kambiz Rahbar discuss the RaLu study examining the safety and efficacy of sequential radiopharmaceutical treatments in metastatic castration-resistant prostate cancer. The discussion highlights how lutetium-PSMA therapy can be safely administered following radium treatment, with outcomes consistent across different treatment sequences and timing intervals. They examine how these...

ctDNA Assay Detects AR Enhancer Alterations Linked to Poor Survival - Russell Pachynski, Aadel Chaudhuri & Christopher Maher

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Oliver Sartor speaks with Russ Pachynski, Chris Maher, and Aadel Chaudhuri about their novel biomarker study in advanced prostate cancer. The discussion centers on their development of a cell-free DNA assay that examines both AR gene and enhancer alterations in mCRPC patients, showing significant prognostic value for treatment outcomes. Dr. Chaudhuri presents their discovery of a stemness signatur...

Optimal Treatment Sequencing in Metastatic Prostate Cancer "Discussion"

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At the 2024 Advanced Prostate Cancer Consensus Conference (APCCC), a panel discussion explores key questions in metastatic prostate cancer treatment. The panel debates mechanisms behind docetaxel's apparent harm in low-volume metachronous disease while emphasizing patient-centered decision-making, acknowledging that while ADT plus ARPI represents a clear standard of care, other treatment decisions...