LAST WEEK TODAY!

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

I took a little time to soak up the holiday season, and I’m guessing the researchers did too! This week didn’t bring much in the way of breaking news, but let’s face it—there’s never a week without some fresh study popping up somewhere. Fight on!
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Among the big changes for 2025, first off, I’ve switched up how I number the newsletters. Secondly, I’m hatching (mostly in my mind right now) a sneaky plan to revamp the site so we can directly—and democratically—fund research that might pique our interest. But I’d like to make sure it’s a clever scheme before I spill all the beans!

As usual, we also have a podcast if you prefer to listen to the newsletter, you can find it HERE.​

Clinical Research

• PHAROS Trial Investigates Novel ACK1 Inhibitor (R)-9bMS​
  The PHAROS trial focuses on men with castration-resistant prostate cancer (CRPC) whose disease has progressed despite enzalutamide or abiraterone. The investigational drug, (R)-9bMS, blocks ACK1—a protein that helps prostate cancer cells survive and spread. This initial study phase emphasizes safety, side effects, and tolerability, while also monitoring whether (R)-9bMS can reduce tumors or slow disease. Researchers will further explore its potential immunomodulatory effects.
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• PT217 Receives FDA Fast Track Designation for Neuroendocrine Prostate Cancer​
  The FDA has granted Fast Track status to PT217 for metastatic de novo or treatment-emergent neuroendocrine prostate cancer (NEPC). PT217 is a first-in-class native IgG-like bispecific antibody targeting DLL3 and CD47. It is being tested in the SKYBRIDGE Phase I/II study to assess safety, tolerability, pharmacokinetics, and preliminary efficacy in patients with advanced, DLL3-expressing cancers. PT217 already holds orphan drug designations for small cell lung cancer and neuroendocrine carcinoma.
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• Emerging Radiopharmaceuticals for Low PSMA-Expressing Prostate Cancer​
  Two agents—67Cu-SAR-bisFAP and 67Cu-SAR-Bombesin—are under development for patients who have little or no Prostate-Specific Membrane Antigen (PSMA) expression. 67Cu-SAR-bisFAP targets fibroblast activation protein (FAP) in the tumor microenvironment and is expected to begin clinical trials by the end of 2025. 67Cu-SAR-Bombesin, which focuses on the Gastrin-Releasing Peptide receptor (GRPr), is already in a Phase 1 trial. Both drugs may be used alongside existing PSMA-oriented therapies to broaden treatment options.
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• KPG-121 Phase 1 Trial Results​
  KPG-121 is a cereblon modulator designed to bind the CRL4-Cereblon (CRBN) complex more strongly than lenalidomide. In a Phase 1 trial of patients with metastatic castration-resistant prostate cancer on stable abiraterone or enzalutamide, 75% experienced treatment-related side effects. Meanwhile, 37.5% achieved partial responses and another 37.5% had stable disease, leading to a 75% disease control rate. Lower doses showed a better safety profile and early hints of clinical benefit.
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• Dietary Supplement Could Supercharge Cancer-Fighting Immune Cells​
  A Phase 1 trial is testing whether beta-hydroxybutyrate (BHB) supplementation can enhance anti-CD19 CAR T cell therapy in relapsed or refractory large B-cell lymphoma. Because CAR T cells favor BHB as an energy source, the hope is to boost their expansion and activity. However, this research is still in its early stages, so no formal dietary or supplement recommendations can be made yet.

Preclinical Research

• Tumor Reversion Research​
  Scientists are investigating ways to reprogram malignant cells into a benign state, rather than destroying them outright. Recent projects include KAIST’s work on a digital twin model of normal cell differentiation, which identified key molecular switches for reversing colon cancer cells, and research at St. Jude Children’s Research Hospital showing that removing certain malignancy-related proteins can strip cells of their cancerous identity. Molecules like TCTP, SIAH1, and PSEN1, along with the tumor microenvironment and non-coding RNAs, play crucial roles. While this approach could reduce side effects and relapse risks, further work is needed to grasp the complex molecular pathways, address the tumor microenvironment, and ensure safe clinical translation.
  (Note: only one preclinical research this week, but potentially a complete solution!)
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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