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PEER-TO-PEER CLINICAL CONVERSATIONS |
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ZNF397 Deficiency: A Key Driver of Lineage Plasticity in Prostate Cancer Therapy Resistance
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Ping Mu, MD
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| Ping Mu discusses his team's paper, "ZNF397 Deficiency Triggers TET2-Driven Lineage Plasticity in AR-Targeted Therapy Resistance in Prostate Cancer," published in Cancer Discovery. Dr. Mu explains that while primary prostate cancer can be managed effectively, resistance to androgen receptor (AR)-targeted therapies in metastatic cases remains a significant challenge.
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| Overcoming Hormone Resistance: ARV-766 in Advanced Prostate Cancer |
| Daniel Petrylak, MD |
| David Crawford discusses with Daniel Petrylak a new approach to treating advanced prostate cancer using a PROTAC agent called ARV-766. Dr. Petrylak explains that PROTACs accelerate the body's natural protein disposal process, targeting the androgen receptor. |
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2024 NCCN Guidelines Update: Metastatic Castration-Resistant Prostate Cancer Treatment
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Rashid Sayyid, MD, MSc, and Zachary Klaassen, MD, MSc
Rashid Sayyid and Zachary Klaassen discuss the 2024 updates to the NCCN guidelines for mCRPC treatment. They review the current management algorithm, emphasizing the importance of confirming castrate status and proper staging.
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| Therapy Resistance and Combination Therapies "Presentation" |
| Johannes Czernin, MD |
| Johannes Czernin explores the challenges of resistance in PSMA-targeted theranostics, advocating for personalized treatments based on dosimetry and strategic combination therapies to enhance efficacy and patient survival. Dr. Czernin calls for a shift in treatment approaches, emphasizing the need for optimized radiation delivery and innovative clinical trials to overcome the limitations observed in current practices. |
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| Loss of CHD1 Promotes Heterogeneous Mechanisms of Resistance to AR-Targeted Therapy via Chromatin Dysregulation - Beyond the Abstract
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| Xiaoling Li, PhD, and Ping Mu, PhD
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| Loss of CHD1 in mCRPC contributes to resistance to AR-targeted therapies by inducing chromatin dysregulation and lineage plasticity, enabling cancer cells to bypass AR dependency. This resistance involves shifts in chromatin accessibility and the activation of alternative transcription factors, with GR inhibition showing potential in overcoming this resistance. This study highlights CHD1's role in therapy resistance and suggests that targeting chromatin dynamics and transcription factors could lead to new treatment strategies.
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| Ectopic JAK-STAT Activation Enables the Transition to a Stem-Like and Multilineage State Conferring AR-Targeted Therapy Resistance - Beyond the Abstract
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| Choushi Wang, and Ping Mu, PhD
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| Aberrant activation of the JAK-STAT signaling pathway is a key driver of lineage plasticity and resistance to AR-targeted therapies in metastatic castration-resistant prostate cancer (mCRPC), especially in cases with TP53/RB1 loss and SOX2 upregulation. This pathway supports the survival of cancer cells with stem-like and multi-lineage traits, making them more adaptable and resistant to treatment.
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| Phase 1 Results and Phase 2 Design - Oral Epi-7386 (Masofaniten) in Combination With Enzalutamide Compared to Enzalutamide Alone in Patients with mCRPC
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| Christos Kyriakopoulos, MD
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| Christos Kyriakopoulos presented results from a phase 1/2 trial evaluating EPI-7386 (masofaniten) in combination with enzalutamide for metastatic castration-resistant prostate cancer (mCRPC). The phase 1 study, which included 18 patients, found the combination to be well-tolerated with a safety profile similar to enzalutamide alone and established the recommended phase 2 dose of masofaniten 600 mg twice daily plus enzalutamide 160 mg once daily.
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Therapy with Metronomic Cyclophosphamide for Previously-Treated Metastatic Castrate-Resistant Prostate Cancer - Beyond the Abstract
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| Nataliya Mar, MD |
| Oral, low-dose metronomic cyclophosphamide (mCyc) has demonstrated effectiveness in treating metastatic prostate cancer, being well-tolerated, cost-effective, and easily accessible due to its off-patent status. Despite its historical efficacy, mCyc has been overshadowed by newer therapies. This article seeks to reintroduce mCyc as a viable treatment option for metastatic castrate-resistant prostate cancer and encourage further research into its potential. |
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