LAST WEEK TODAY!

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

Hello fellow warriors! Research seems to have slowed down for August, but what we have this week is really good. 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 3 Trial: Pluvicto Reshaping First-Line Metastatic Therapy
  ​A significant regulatory approval has brought radioligand therapy into the first-line setting for metastatic hormone-sensitive prostate cancer (mHSPC). Pluvicto (lutetium Lu-177 vipivotide tetraxetan), which targets the prostate-specific membrane antigen (PSMA), is now approved for use in combination with standard androgen deprivation therapy and androgen receptor pathway inhibitors. This shift is supported by the Phase 3 PSMAddition trial, which demonstrated that this combination therapy resulted in a 33% reduction in the risk of disease progression or death compared to standard care alone. This milestone highlights a move toward intensifying treatment earlier in the disease trajectory to improve long-term outcomes.​
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• Phase 1 Trial: Deep Responses Observed with 67Cu-SAR-bisPSMA
  ​Encouraging news clinical data from the SECuRE trial indicates that the radioligand therapy 67Cu-SAR-bisPSMA can produce profound anti-tumor activity in patients with heavily pre-treated metastatic castration-resistant prostate cancer (mCRPC). In a cohort of 19 patients receiving an 8 GBq dose, five participants achieved either a complete response or undetectable disease based on PSA levels and imaging. Notably, 63% of patients experienced at least a 50% reduction in PSA, and more than one-quarter achieved a PSA90 response.​
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• Phase 1/2 Trial: FDA Clears Personalized Immunotherapy Bria-PROS+
  ​The FDA has cleared the start of a Phase 1/2a clinical study for Bria-PROS+, an investigational “off-the-shelf” cellular immunotherapy for advanced prostate cancer. This treatment uses a personalized matching strategy based on a patient’s human leukocyte antigen (HLA) characteristics to enhance the immune system’s ability to recognize and attack malignant cells. Preclinical research suggests the therapy works through a multipronged activation of naïve T cells, dendritic cells, and natural killer cells, potentially reducing the risk of immune escape.
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• B7-H3: A Stable Target for Advanced Disease States
  ​Landmark research utilizing the JHU-PANORAMA single-cell atlas has reframed B7-H3 (CD276) as a premier targetfor combinatorial therapy across the full continuum of prostate cancer. Unlike common targets like PSMA, which can decrease when the cancer becomes resistant to hormone therapy, B7-H3 is negatively regulated by androgen receptor (AR) signaling. This means its expression remains high and stable even in AR-negative and neuroendocrine phenotypes. The study suggests that B7-H3 can serve as an anchor for bispecific and dual-ADC strategies, achieving high combinatorial scores with other targets like TROP-2 and KLK2 to limit therapeutic escape.
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Preclinical Research & Reviews

• Boosting ADC Efficacy by Inhibiting BCL-XL
  ​Researchers at UCLA have identified a promising method to improve the effectiveness of antibody-drug conjugates (ADCs) by pairing them with drugs that block the protein BCL-XL. Because BCL-XL typically helps cancer cells survive by blocking programmed cell death, inhibiting it makes the cells far more vulnerable to the DNA-damaging payloads delivered by ADCs. Tumor analysis revealed that three major ADC targets (B7-H3, PSMA, and STEAP1)often appear on the same cancer cells, suggesting that researchers can strengthen existing therapies by matching the right targets with this BCL-XL-blocking chemistry.
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• Viagra and Statins: A Potential Synergy to Stop Metastasis
  ​A recent study suggests that sildenafil (the active ingredient in Viagra) may prevent cancer cells from spreading by disrupting cholesterol trafficking inside the cells. By blocking the PDE5 enzyme, sildenafil increases cGMP, which eventually interferes with the cells’ ability to access the cholesterol necessary to break away from primary tumors and colonize distant organs. Analysis of long-term health records showed that cancer patients taking sildenafil had better survival outcomes, an association that was even stronger when combined with statins. While these findings provide a new line of investigation into the metabolic state of cancer, they require validation through formal clinical trials (hard proof).
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And…that’s all folks! For today at least!
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Have a great weekend!

Max