LAST WEEK TODAY!

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

HAPPY NEW YEAR!ÂBefore we dive into the latest news from prostatewarriors.com I want to wish you all a great 2025!
The seventh and final newsletter of 2024 is here, bringing you fresh insights and renewed hope.

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

Clinical Research

• Bispecific Antibodies: JNJ-87189401 and JNJ-78278343​
  A Phase 1, first-in-human, open-label trial is evaluating the safety, tolerability, and preliminary efficacy of combining JNJ-87189401 and JNJ-78278343 in patients with advanced prostate cancer. JNJ-87189401 targets PSMA on prostate cancer cells and CD28 on T cells, enhancing T-cell activation. JNJ-78278343 targets KLK2, a protein abundant in prostate cancer, and CD3, activating T cells to attack KLK2-expressing cells. Combining these agents may enhance T-cell activation and yield deeper, more durable tumor responses.
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• INV-9956​
  A Phase 1 multi-center, open-label trial is recruiting adult patients with advanced metastatic castration-resistant prostate cancer (mCRPC). INV-9956 is an orally available, highly selective CYP11A1 inhibitor that reduces androgen production, targeting advanced-stage cancers resistant to conventional therapies. Preclinical studies demonstrated that INV-9956 suppresses the proliferation of prostate cancer cell lines harboring drug-resistant AR ligand-binding domain mutations.
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• QXL138AM​
  A Phase 1 trial is recruiting participants to evaluate this masked immuno-cytokine (MIC) for prostate cancer and other CD138-expressing tumors. QXL138AM combines interferon alpha 2 (IFNα2) with an antibody targeting CD138, using a masking mechanism to minimize systemic side effects. This design allows selective activation within the tumor microenvironment, enhancing its precision and safety. Preclinical studies demonstrated 69% tumor growth inhibition in prostate cancer models and significant tumor inhibition in multiple myeloma murine models, showcasing its therapeutic potential across cancer types.
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• AVA6000​
  A Phase 1 trial is underway to evaluate this peptide drug conjugate (PDC) that delivers doxorubicin directly to tumors with high Fibroblast Activation Protein (FAP) activity. AVA6000 is a prodrug activated by FAP enzymes in the tumor microenvironment, allowing targeted treatment of advanced prostate cancer. FAP is expressed in 50%-80% of advanced prostate cancers, particularly aggressive forms.

Preclinical Research

• Nanoparticle Therapy​
  Biodegradable nanoparticles are being developed to deliver two FDA-approved drugs simultaneously to tumor cells. This approach uses a protein called P-selectin to target cancerous tissue while sparing healthy cells. Early testing in other solid tumors demonstrated improved efficacy, delayed progression, and a survival advantage, all with reduced side effects.
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• PIM-1 Kinase Inhibition Through Drug Repurposing​
  Screening efforts identified rifaximin, an FDA-approved drug, as a PIM-1 kinase inhibitor. This discovery highlights its potential to inhibit tumor progression in prostate cancer, particularly when combined with existing therapies. Rifaximin’s established safety profile supports its exploration in preclinical and clinical cancer studies.
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• LIG1 Targeting​
  CRISPR/Cas9 screening identified LIG1 as a potential synthetic lethality partner for PARP inhibitors. Targeting LIG1 alongside PARP causes a synergistic effect leading to cancer cell death. This approach has demonstrated promising results in multiple cancer types, including prostate cancer.
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• Ferroptosis​
  Research highlights the potential of ferroptosis, an iron-dependent form of programmed cell death, as a therapeutic target for CRPC. Ferroptosis involves disrupted iron metabolism and lipid peroxidation. Agents like erastin and RSL3 are being explored to induce ferroptosis in prostate cancer cells.
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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