LAST WEEK TODAY!

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

Hi, fellow fighters! This week, the updates are primarily in clinical research, we could call it the Nectin-4 week!

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

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Clinical Research

• Phase 2 Trial: Opaganib Plus Darolutamide for mCRPC​
  A clinical trial is assessing the combination of opaganib, a selective sphingosine kinase-2 inhibitor, and darolutamide, a next-generation androgen receptor antagonist, for metastatic castration-resistant prostate cancer (mCRPC). Opaganib modulates the tumor microenvironment and inhibits tumor cell proliferation by targeting sphingolipid metabolism, which plays a role in cancer progression. Darolutamide prevents androgen receptor activation, a major driver of prostate cancer. However, patients previously treated with potent androgen receptor pathway inhibitors (ARPIs) will be excluded.​
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• Pioneering Korean Trial: Radioligand Therapy + Immunotherapy for Advanced Prostate Cancer​
  A phase 1 trial in Korea is investigating the combination of Lutetium (177Lu) DGUL, a PSMA-targeted radioligand therapy, with anti-PD-1 therapy (Keytruda, pembrolizumab) in advanced prostate cancer. Lutetium-177 PSMA therapy delivers targeted radiation to PSMA-positive cancer cells, selectively destroying them, while anti-PD-1 immunotherapy enhances the immune system’s ability to recognize and attack tumors. Radiotherapy may increase tumor antigen presentation, making cancer cells more visible to the immune system and improving response to checkpoint inhibitors. If successful, this trial will expand into a phase 2 study in the U.S.​
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• Phase 1 Clinical Trial Recruiting: HLD-0915 – A RIPTAC-Based Therapy​
  A phase 1 trial is recruiting for HLD-0915, an orally bioavailable Regulated Induced Proximity Targeting Chimera (RIPTAC)Âfor mCRPC. RIPTAC technology forces proximity between two proteins, leading to targeted degradation or activation, which enables precise targeting of cancer-associated proteins while minimizing off-target effects.
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• Phase 1 Trial Will Soon Start: ACE-232 – A Novel CYP11A1 Inhibitor​
  A phase 1 clinical trial for ACE-232, a CYP11A1 inhibitor, is set to begin in April 2025. CYP11A1 is the rate-limiting enzyme in steroidogenesis, including androgen synthesis. Inhibiting this enzyme could reduce intra-tumoral androgen production, which fuels prostate cancer progression despite systemic androgen deprivation therapy (ADT). The trial will evaluate safety, tolerability, pharmacokinetics, and preliminary efficacy.
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• Phase 1 Trial: CRB-701 – A Nectin-4 Targeting Antibody-Drug Conjugate (ADC)​
  A phase 1/2 trial (NCT06265727) is evaluating CRB-701, an antibody-drug conjugate (ADC) designed to target Nectin-4, a cell adhesion molecule overexpressed in certain solid tumors, including prostate cancer. ADCs combine the specificity of an antibody with a potent cytotoxic agent, ensuring selective delivery to tumor cells while sparing normal tissue. Further data is expected at the 2025 ASCO GU Cancers Symposium in February 2025 (well…next week!)
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• Nectin-4-Targeting Therapies: LY4052031 and LY4101174​
  Two additional Nectin-4-targeting ADCs, LY4052031 and LY4101174, are in a phase 1a/1b trial. The study involves dose-escalation to determine the maximum tolerated dose, followed by a dose-optimization phase to assess efficacy. These therapies aim to broaden the treatment landscape for Nectin-4-positive tumors, following the success of enfortumab vedotin, an FDA-approved Nectin-4 ADC in bladder cancer.

Preclinical Research

• CRISPR Use Against Tumors – Metabolic Reprogramming to Starve Cancer​
  Researchers at UCSF are using CRISPR gene-editing to transform white fat cells into “beige” fat cells, which burn calories instead of storing them. These engineered fat cells consume excess nutrients, effectively starving cancer cells of the metabolic resources they need to grow. This represents a non-toxic metabolic intervention that could complement traditional cancer treatments.
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• Adhibin as an Anti-Metastatic Agent, Breakthrough of The Week​
  Adhibin, a synthetic small molecule, inhibits cancer metastasisÂ(in vitro and in vivo) by targeting the Rho GTPase signaling pathway, which regulates cytoskeletal dynamics and enables cancer cells to migrate and invade new tissues. By blocking this pathway, Adhibin prevents metastasis, making it a potential candidate for combination therapies with chemotherapy or immunotherapy.
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• Repurposing Non-Cancer Drugs for Oncology​
  A computational approach, published on Nature, has been developed to identify non-oncology drugs with potential anticancer effects. This AI-drivenÂdrug repurposing technique matches existing drugs to specific cancers based on molecular profiles. This method accelerates drug development by bypassing early-stage safety trials and reduces costs compared to traditional drug discovery. Notably, applying this method to approximately 5000 cancer samples indicated that >30% might respond to at least one non-oncology drug.​
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And…that’s all folks! For today at least!
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Have a great weekend!

Max