Advanced Prostate Cancer VL

Canonical Androgen Response Elements in Prostate Cancer Growth Suppression - Christopher Barbieri

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Christopher Barbieri joins Andrea Miyahira to discuss research exploring how androgen receptor (AR) response elements function in prostate cancer. His team's work reveals distinct transcriptional programs controlled by AR, showing that canonical AR response elements actually suppress tumor growth while maintaining normal prostate cell differentiation. Using artificial transcription factors, the te...

ADT Remodels the Tumor Microenvironment from Immunologically Cold to Hot - Matthew Dallos

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Matthew Dallos joins Andrea Miyahira to discuss research examining how androgen deprivation therapy (ADT) reshapes the immune landscape in localized prostate cancer. Through analysis of clinical trial samples, Dr. Dallos reveals that ADT rapidly transforms traditionally "cold" prostate tumors into immunologically "hot" environments within days of treatment. The work demonstrates complex immune cha...

ASCL1 and FOXA2 in Neuroendocrine Prostate Cancer - Shaghayegh Nouruzi

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Shaghayegh Nouruzi joins Andrea Miyahira to discuss her recent JCI Insight publication exploring the role of transcription factors in prostate cancer lineage plasticity and neuroendocrine differentiation. She details how ASCL1 shows stage-specific functions, initially driving lineage plasticity but later cooperating with FOXA2 to maintain the terminal neuroendocrine phenotype. The research reveals...

CDK12 Mutation Types and PARP Treatment Effectiveness - Jonathan Chou

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Jonathan Chou discusses research on targeting CDK12-deficient prostate cancer with PARP inhibitors. Through analysis of CDK12 mutations, which occur in 5-8% of advanced prostate cancers, Dr. Chou demonstrates how different mutation types exhibit varying sensitivities to PARP inhibition. His work reveals that biallelic mutations show greater treatment response compared to monoallelic or gene rearra...

PARP Inhibitor Resistance Mechanisms in Prostate Cancer - Johann De Bono

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Johann De Bono joins Andrea Miyahira to discuss his team's decade-long research on PARP inhibitor resistance in advanced prostate cancer, recently published in Cancer Cell. Drawing from extensive analysis of plasma samples and circulating tumor cells from the TOPARP trials, Dr. De Bono reveals that resistance primarily develops through restoration of homologous recombination repair function in BRC...

Universal Germline Genetic Testing for Prostate Cancer Patients - Neal Shore & Sarah Young

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Neal Shore and Sarah Young join Zachary Klaassen to discuss a JCO Oncology Practice publication advocating for universal germline genetic testing in prostate cancer patients. The discussion highlights that 8-14% of unselected prostate cancer patients carry pathogenic variants, with clinical utility across all disease stages from early detection to treatment selection. Despite the proven benefits f...

Physician Decision Making & Combination Therapies in Metastatic Prostate Cancer - Neeraj Agarwal

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Neeraj Agarwal discusses a JAMA Network Open study examining physicians' reasons for or against treatment intensification in metastatic prostate cancer. The study surveys 107 US physicians managing over 600 patients, revealing significant underutilization of combination therapies despite strong evidence supporting their use. Key barriers include concerns about side effects, quality of life impact,...

AR EcDNA Discovery in Advanced Prostate Cancer Study - George Zhao

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George Zhao joins Andrea Miyahira to discuss research examining three-dimensional genome organization in metastatic prostate cancer. The study integrates multi-omic data including RNA-seq, whole-genome sequencing, and Hi-C sequencing. Their key finding reveals that approximately one-third of samples show disrupted genomic organization around the androgen receptor (AR) gene, which they discover is...

Machine Learning Stemness Signature for Prostate Cancer - Agustina Sabater & Geraldine Gueron

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Andrea Miyahira speaks with Geraldine Gueron and Agustina Sabater about a paper on neuroendocrine prostate cancer. The discussion focuses on the development of a seven-gene stemness signature that predicts cancer progression. Using machine learning algorithms and multiple data sets, they create a risk-score model that shows significant prognostic value across different stages of prostate cancer, i...

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...