LAST WEEK TODAY!

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

Hi fellow warriors!
​A quick note from me: our newsletter runs on Kit.com, which costs $290/year to keep going. If you enjoy these updates and would like to chip in to help cover the renewal, you can do so here, or send me a message if you want to use a different system. No pressure at all!
While we await the new findings to be presented at ESMO 2025, we have two interesting clinical studies and three preclinical studies that I’m sure you will find engaging! 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.
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Clinical Research

• Phase 2 Trial: PAM50 Subtyping Predicts Response to Apalutamide in Recurrent Prostate Cancer​
  The phase II BALANCE trialexplored whether genomic subtyping could identify men with recurrent prostate cancer most likely to benefit from adding apalutamide to salvage radiation therapy after prostatectomy. Using the PAM50 gene expression test, tumors were classified by molecular subtype, focusing on the luminal B group. Among 295 patients enrolled, those with luminal B tumors (about 43% of the cohort) showed significant benefit from apalutamide, with five-year biochemical progression-free survival of 72.4% compared to 53.9% with placebo, and five-year metastasis-free survival of 94.7% versus 81.8%. Patients with non–luminal B tumors saw no improvement. The findings indicate that PAM50 subtyping can guide more selective use of hormonal therapy, reserving apalutamide for patients most likely to respond.
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• Phase 2 Trial: Multi-Modal Therapy Shows Promise in Poly-Metastatic Prostate Cancer​
  A prospective interim study examined the combination of enzalutamide, denosumab, local radiotherapy, and metastasis-directed therapy in men with poly-metastatic castration-resistant prostate cancer, defined as having four or more bone lesions. Twenty patients were enrolled and followed for a median of 18 months. Results showed one-year radiographic progression-free survival of 100% and overall progression-free survival of 84.4%, with 85% of patients achieving at least a 90% decline in PSA levels. Half of the participants maintained PSA levels below 0.2 ng/mL, a marker associated with improved long-term outcomes. The findings support the feasibility and safety of an aggressive, multimodal approach for high-volume metastatic disease, with outcomes comparable to or better than historical data from large trials involving less advanced cases.
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Preclinical Research & Reviews

• DOLPHIN AI Detects Hidden Cancer Biomarkers in Single Cells​
  DOLPHIN, an artificial intelligence platform developed at McGill University, has set a new standard for identifying hidden cancer biomarkers in single-cell data. Unlike conventional methods that analyze genes as single units, DOLPHIN examines RNA sequencing data at the exon and splice-junction level. In cancer samples, the system uncovered more than 800 cancer-associated markers missed by traditional approaches, effectively distinguishing between high-risk and less aggressive patient groups. By generating detailed molecular profiles of individual cells, DOLPHIN enables earlier and more precise disease characterization. This capability could streamline drug discovery by allowing researchers to test therapies in silico before moving to preclinical trials.
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• Epigenetic Editing Achieves Long-Term Gene Silencing Without DNA Alteration​
  Advances in epigenetic editing have produced durable tools for controlling gene activity without altering DNA sequences.A recent Nature Biotechnology study described the development of TALE-based EpiReg-T regulators delivered through lipid nanoparticles to target PCSK9, a key gene in cholesterol metabolism. In nonhuman primates, a single dose of this system achieved over 90% silencing of PCSK9 in the liver, an effect that persisted for nearly a year. The lipid nanoparticle delivery avoided complications associated with viral vectors. Such epigenetic regulators offer potential for cancer therapy by allowing precise and reversible control of oncogenes or tumor suppressor genes, combining specificity with a lower risk of genomic damage.
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• Ant2 Inhibition Enhances T Cell Anti-Tumor Activity​
  Blocking Ant2 has emerged as a promising strategy to enhance immune responses against cancer. Ant2 (adenine nucleotide translocase 2) is a mitochondrial transporter that regulates how T cells generate and use energy, shaping their metabolic fitness during immune activation. In prostate cancer, Ant2 is markedly overexpressed, often up to four times higher than in normal tissue, where it contributes to tumor growth and therapy resistance. Experimental inhibition or silencing of Ant2 in prostate cancer models suppresses cell proliferation, promotes apoptosis, and increases sensitivity to agents such as TRAIL. These findings suggest that targeting Ant2 could serve as a foundation for metabolic immunotherapy aimed at strengthening the body’s natural anti-tumor defense.
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And…that’s all folks! For today at least!
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Have a great weekend!

Max