LAST WEEK TODAY!

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

Hello fellow warriors! We are getting closer to the end of the year. Will we have some new amazing findings before 2027?
Thank you for your support! 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.

Clinical Research

• Phase 1/2 Trial: ALT-100 Targeting the Bone Microenvironment​
  The ALTAR-100 trial is a Phase 1/2 clinical study evaluating ALT-100, an experimental monoclonal antibody designed to target the biological environment surrounding bone metastases rather than attacking cancer cells directly. By targeting extracellular nicotinamide phosphoribosyltransferase (eNAMPT) and inhibiting the eNAMPT/TLR4 pathway, the treatment aims to disrupt inflammatory signaling and tissue remodeling that foster tumor survival in bone tissue. The trial is enrolling 42 patients with bone-predominant metastatic castration-resistant prostate cancer (mCRPC) resistant to androgen pathway therapies.
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• Phase 1/2 Trial: TroFuse-01A Testing a TROP2-Targeted ADC
  ​The TroFuse-01A trial is a Phase 1/2 study investigating sacituzumab tirumotecan (MK-2870), an experimental antibody-drug conjugate (ADC) directed against TROP2, a cell-surface protein overexpressed in metastatic prostate cancer. The therapy delivers a topoisomerase I inhibitor payload directly to TROP2-expressing cells to induce lethal DNA damage. The trial evaluates sacituzumab tirumotecan as monotherapy at two dose levels, in combination with opevesostat (an oral inhibitor of steroid hormone synthesis), and alongside a docetaxel chemotherapy comparator arm in patients with mCRPC.
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• Phase 2 Trial: Enzomenib Oral Menin Inhibitor
  ​A Phase 2 clinical trial is investigating enzomenib (DSP-5336), an experimental oral menin inhibitor that targets epigenetic gene regulation mechanisms involving KMT2A rather than traditional androgen receptor signaling. Patients with mCRPC receive twice-daily oral doses of enzomenib in 28-day treatment cycles while continuing ADT. Uniquely, the trial’s primary endpoint measures metabolic response using FDG-PET imaging to assess reductions in tumor metabolic activity, complemented by PSMA-PET imaging to evaluate treatment effects across metastatic sites.
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Preclinical Research & Reviews

• FDA Guidance on Plug-and-Play Gene Editing
  ​A draft guidance released by the U.S. FDA proposes a new regulatory framework, the Individualized Feature Space (IFS), to streamline the development of personalized CRISPR-based genome-editing therapies. This “plug-and-play” framework allows multiple target-specific therapeutic variants of an established platform to be evaluated under a single Biologics License Application (BLA), reducing redundant testing costs. In advanced prostate cancer, this strategy could enable adaptive treatments that pair regular liquid biopsies with rapidly adjusted gene-editing vectors to target emerging resistant clones over time.
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• Liquid Biopsies for Tracking PSMA Radioligand Therapy Resistance
  ​A prospective study of 78 mCRPC patients published in BMC Cancer demonstrates that circulating tumor DNA (ctDNA) liquid biopsies can effectively monitor disease progression and resistance during actinium-225 and lutetium-177 PSMA-617 radioligand therapy. Elevated ctDNA levels correlated closely with PSA changes and signaled a significantly higher risk of disease progression (hazard ratio of 4.9). Additionally, tracking copy-number alterations in tumor suppressor and DNA repair genes (PTEN, RB1, BRCA2, ATM) showed that higher alteration burdens correlated with shorter median overall survival (8.3 vs. 13.8 months), offering valuable insights into resistant subclone dynamics.
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• MS4A8 as a Potential Driver of Bone Metastases
  ​A preclinical study published in Cell Death Discovery identified MS4A8, a protein carried by cancer cell-derived exosomes, as a key driver of prostate cancer bone metastasis. Exosomal MS4A8 stimulates osteoclast activity and bone degradation via RANKL upregulation and activation of the NF-κB and AKT signaling pathways. This creates a vicious cycle of tissue remodeling and tumor expansion in the bone niche, highlighting MS4A8 and its downstream signaling cascades as promising targets for therapeutic disruption.
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• Three-Gene Blood Test for Predicting Hormonal Therapy Resistance
  ​Published in Frontiers in Oncology, a study of 157 metastatic hormone-sensitive prostate cancer (mHSPC) patients developed a blood-based gene expression model (SLC25A39, SLC6A8, YBX3) to predict early resistance to androgen deprivation and receptor pathway therapies. The three-gene biomarker achieved high predictive accuracy (AUC of 0.89 in development, 0.83 in validation), identifying high-risk patients who faced a 17.19-fold higher risk of progressing to mCRPC with a median progression-free time of 15.5 months. Notably, SLC6A8 was also found to regulate cellular creatine transport, linking tumor energy metabolism directly to cancer progression.​

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And…that’s all folks! For today at least!
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Have a great weekend!

Max