LAST WEEK TODAY!

A summary of what was published on ProstateWarriors.com during the past week

Hello fellow warriors! New weapons on the way! Stay strong and fight on!

As usual, we also have a podcast if you prefer to listen to the newsletter, you can find it HERE. I tried a different approach for this podcast, with more detailed explanations. Let me know if you prefer a more condensed version.​

Clinical Research

• Phase 3 Trial: Himalayas-1 Rinzimetostat and Darolutamide
  ​The Himalayas-1 study is a global Phase 3 registrational trial evaluating the combination of rinzimetostat (ORIC-944) and darolutamide in patients with metastatic castration-resistant prostate cancer (mCRPC) who were previously treated with abiraterone. Rinzimetostat is designed to block the PRC2 complex by targeting its EED subunit, an epigenetic mechanism linked to hormone therapy resistance and aggressive disease growth. This pivotal trial follows encouraging Phase 1b data, which demonstrated a 59% PSA50 response rate and a manageable safety profile consisting mostly of low-grade fatigue and gastrointestinal symptoms. The primary objective of the study is to improve radiographic progression-free survival, potentially offering a new biomarker-agnostic oral treatment option for the post-abiraterone setting.​
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• Phase 2 Trial: Adaptive PSMA-PET–Guided TLX597-Tx​
  The OPTIMAL-e trial is a Phase 2 pilot study investigating a personalized, adaptive dosing strategy using the radioligand 177Lu-DOTA-HYNIC-panPSMA (TLX597-Tx) for men with metastatic hormone-sensitive prostate cancer (mHSPC). Unlike fixed-cycle regimens, this approach uses PSMA-PET imaging to decide when to pause or resume treatment based on the presence of PSMA-avid disease. The goal of this flexible schedule is to maintain long-term disease control while reducing the patient’s cumulative radiation exposure, thereby limiting potential damage to the bone marrow and other organs.​
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• Phase 1 Trial: SHY-ONC6 Proteasome-Modulating Therapy
  ​This Phase 1 study evaluates SHY-ONC6, a novel therapeutic that targets the proteasome, the cell’s protein quality-control system, in a manner distinct from earlier inhibitors like bortezomib. Because prostate cancer cells rely heavily on this system to manage stress and avoid cell death, SHY-ONC6 may produce a unique antitumor effect even in cases where older proteasome-based approaches have failed. Researchers believe this mechanism is particularly relevant for addressing PTEN-deleted mCRPC, a subtype known for its therapeutic resistance.​
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Preclinical Research & Reviews

• CRISPR RNA Editing for Immune-Cold Tumors
  ​A new RNA-targeted CRISPR technology called 3′UTRCES has been developed to make “invisible” prostate tumors visible to the immune system. Many prostate cancers hide from T cells by reducing MHC class I “ID badges” on their surface, a process driven by an overabundance of the protein SPSB1. This CRISPR tool works at the RNA level (without permanently editing DNA) to lower SPSB1 levels and restore MHC class I expression. In mouse models, this technology effectively turned “immune-cold” tumors into “hot” ones, significantly increasing their sensitivity to immune checkpoint therapy.
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• Combining Radioligand Therapy with CAR-T Cells
  ​Preclinical research has identified that radioligand therapy (RLT) can function as a powerful immune primer to enhance the effectiveness of CAR-T cell therapy in mCRPC. By inducing immunogenic cell death and remodeling the myeloid compartment, RLT shifts the tumor microenvironment from an immunosuppressive state to a pro-inflammatory one. When 177Lu-PSMA-617 was combined with PSCA-targeted CAR-T cells, the combination significantly improved tumor control and survival compared to either treatment used alone, suggesting a potent new strategy for overcoming antigen heterogeneity.

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And…that’s all folks! For today at least!
Please let me know if there is anything I can improve in my newsletters, and let me know if you have enjoyed the podcast.

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Have a great weekend!

Max