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PEER-TO-PEER CLINICAL CONVERSATIONS |
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| The Efficacy and Resistance-Breaking Potential of EPI-7386 Masofaniten in Castration-Resistant Prostate Cancer |
Andrew Laccetti, MD, MS
Zach Klaassen engages Andrew Laccetti in a discussion about Masofaniten (EPI-7386), a pioneering anti-androgen therapy targeting the N-terminal domain of the androgen receptor, aimed at overcoming resistance mechanisms observed with current prostate cancer treatments. |
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Intrapatient Heterogeneity in Prostate Cancer: A Deep Dive into Androgen Receptor Alterations
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Gerhardt Attard, MD, Ph.D., FRCP
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| In this conversation, Andrea Miyahira hosts Gerhardt Attard to discuss a publication in Nature Communications, specifically focusing on the genomic architecture of lethal prostate cancer clones.
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| Loss of SYNCRIP Unleashes APOBEC-Driven Mutagenesis, Tumor Heterogeneity, and AR-Targeted Therapy Resistance in Prostate Cancer |
| Ping Mu, Ph.D. |
| Andrea Miyahira speaks with Ping Mu about his group's paper and research focusing on the role of SYNCRIP in controlling APOBEC-driven mutagenesis in prostate cancer. Dr. Mu explains that the loss of SYNCRIP leads to a break in the mechanism controlling this mutagenesis driver, resulting in prostate cancer gaining resistance to AR therapy. |
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| A Phase 1/2 Study of ONCT-534, a Dual-Action Androgen Receptor Inhibitor in Patients with Metastatic Castration-Resistant Prostate Cancer
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| Evan Yu, MD
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| Evan Yu unveils a promising Phase 1/2 study of ONCT-534, a novel Dual-Action Androgen Receptor Inhibitor (DAARI), targeting metastatic castration-resistant prostate cancer. Unlike current therapies, ONCT-534 aims to overcome resistance mechanisms by inhibiting AR function and degrading the AR protein, offering hope for patients resistant to existing treatments.
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| Phase 1/2 Trial of Oral EPI-7386 in Combination with Enzalutamide Compared to Enzalutamide Alone in mCRPC Subjects: Current Phase 1 Results
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| Andrew Laccetti, MD, MS
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| Andrew Laccetti presents the results of a phase 1/2 trial of oral EPI-7386 in combination with enzalutamide compared to enzalutamide alone in metastatic castration-resistant prostate cancer. EPI-7386 is a next-generation antiandrogen designed to inhibit androgen receptor activity by binding the N-terminal domain. The trial enrolled mCRPC patients on androgen deprivation therapy who were naive to second-generation antiandrogens.
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| Androgen Receptor Addiction in Prostate Cancer, Breaking the Habit
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| Evan Yu, MD
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| Androgen receptor (AR) signaling is the most important driver of prostate cancer initiation, development, and progression, even into the castration-resistant state. Androgen deprivation therapy is the original “targeted therapy” in oncology. The next-generation androgen- and AR-targeted agents, such as abiraterone acetate, enzalutamide, apalutamide, and darolutamide further prove the concept that AR signaling remains critical in even later disease states.
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| The Androgen Receptor Remains the Main Driver of Disease: Towards Third-Generation Inhibitors? |
| Alice Bernard-Tessier, MD |
| Alice Bernard-Tessier discusses the potential of third-generation inhibitors of the androgen receptor in advanced prostate cancer. While second-generation androgen receptor signaling inhibitors have shown considerable benefit, resistance is inevitable. Resistance mechanisms include androgen receptor genomic alterations and alternative ligands. |
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| State of the Art Lecture: Future Perspectives in the Management of mHSPC: Where Are We Heading To? |
| Eugen Jan Karol Axcrona, MD, Ph.D. |
| Eugen Jan Karol Axcrona discusses the future perspectives in the management of metastatic hormone-sensitive prostate cancer. He highlights the benefit of adding androgen receptor blockades to androgen deprivation therapy (ADT) and discusses recent trials showing improved outcomes with the addition of various treatments to ADT, such as docetaxel and androgen receptor inhibitors. |
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| Prospective Assessment of AR Splice Variant and Multi-Biomarker Expression on Circulating Tumor Cells of mCRPC Patients Undergoing Androgen Receptor Targeted Agents: Interim Analysis of the PRIMERA Trial |
| Giulio Francolini, Mauro Loi, Lucia Pia Ciccone et al. |
| In this manuscript, the authors report the results of a prospective trial performed at their institutions, exploring the prognostic value of CTCs in patients affected by mCRPC undergoing treatment with 1st-line androgen receptor-targeted agents (either abiraterone or enzalutamide). Of note, CTC expression of PSA, PSMA, androgen receptor, and androgen receptor splice variant 7 was recorded. |
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| The Impact of AR-V7 and Other Androgen Receptor Splice Variant Expression on Outcomes of Post-Prostatectomy Salvage Therapy
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| Keisuke Otani MD, Ph.D.
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| Researchers investigated the influence of androgen receptor splice variants on salvage therapy outcomes in patients with prostate cancer who had undergone radical prostatectomy. The study found that patients with AR-V7-positive tumors had significantly shorter biochemical progression-free survival compared to those with AR-V7-negative tumors, suggesting AR-V7 presence may predict inferior outcomes to salvage radiotherapy with androgen deprivation therapy.
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