LAST WEEK TODAY!

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

Hi fellow warriors! This edition of the newsletter will also be mainly focused on preclinical studies that are approaching human trials. The AACR 2026 meeting begins in about twenty days, and updates on ongoing clinical trials will not be available until just a few days before it starts. But you’ll see that you won’t be disappointed with this newsletter either. 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

• Christopher Sweeney on mHSPC Treatment Standards
  ​Christopher Sweeney’s ASCO GU 2026 presentation highlights how landmark trials like CHAARTED and ENZAMET have revolutionized the management of metastatic hormone-sensitive prostate cancer (mHSPC). Modern combination therapies (doublet and triplet therapies) have roughly doubled 8-year overall survival to approximately 50%, compared to just 25% with ADT alone in the 1990s. Data from the CHAARTED trial specifically showed that adding docetaxel significantly improved survival in patients with high-volume disease, while deep PSA responses (less than 0.2 ng/mL) in the ENZAMET trial served as a robust prognostic marker for long-term survival. Sweeney emphasizes that ADT plus an ARPI should be the standard backbone for eligible patients, with chemotherapy reserved primarily for those with high-volume disease who can tolerate it.​
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• Phase 1 Trial: NEOK001 Development for Advanced Cancers
  NEOK001 (also known as ABL206) is a novel bispecific antibody–drug conjugate (ADC) scheduled to enter Phase 1 clinical trials in early 2026. This experimental drug simultaneously targets two proteins, B7‑H3 and ROR1, delivering a potent topoisomerase I inhibitor (exatecan) directly to tumor cells that co-express these markers. Because B7-H3 and ROR1 are overexpressed in aggressive, treatment-resistant prostate cancers but are limited in normal tissues, this dual-targeting strategy aims to maximize efficacy while reducing off-target toxicity. In animal models, NEOK001 produced tumor regression in over half of the tested patient-derived xenografts, demonstrating significant promise for aggressive prostate cancer variants.​
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• Phase 1 Trial: ASTX295 and the MOS101 Clinical Program
  ASTX295 is an experimental MDM2 antagonist designed to reactivate the p53 tumor-suppressor protein in cancers where the gene is intact but switched off. While its single-agent activity in early clinical work was modest, combining it with the PARP inhibitor olaparib has shown substantial synergy. This combination, featured in the MOS101 clinical program, is particularly effective in BRCA2-mutant, TP53-wild-type tumors. By blocking both DNA repair and the MDM2-p53 interaction, the treatment pushes stressed cancer cells toward programmed cell death (apoptosis) rather than simple cell-cycle arrest, leading to more durable tumor control in preclinical models.​
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• Phase 1 Trial: Bvax Personalized B-Cell Therapy
  Bvax is an innovative immunotherapy currently being tested in a Phase 1 trial for glioblastoma, with the potential for adaptation to prostate cancer. The treatment involves activating a patient’s own B cells, loading them with tumor antigens, and reinfusing them to stimulate a targeted immune attack. In mouse models of immune-excluded prostate cancer, Bvax treatment reduced tumor volume by 68% and successfully increased immune cell infiltration into the tumor tissue. This approach is specifically designed to overcome the challenges of “cold” tumors that typically do not respond to existing checkpoint inhibitors.​
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Preclinical Research & Reviews

• Retrospective Study of Alpha vs. Beta-Emitting PRRT
  ​A retrospective analysis of patients receiving peptide receptor radionuclide therapy (PRRT) examined the immune-gene changes triggered by beta-emitting (177Lu-DOTATATE) versus alpha-emitting (212Pb-DOTAMTATE) drugs. The study found that alpha-emitter therapy induced a more coherent and intense immune-activation signature in responders, particularly in pathways related to inflammation and cell death. While both types of radiation caused a drop in circulating lymphocytes, the alpha-emitter stimulated an early inflammatory and monocyte-driven response that correlated with treatment success. This research suggests that whole-blood RNA analysis could eventually help predict which patients will benefit most from specific types of PRRT.​
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• Observational Study on Pre-Diagnostic Vitamin D and Survival
  ​A massive international analysis of over 12,000 men indicates that higher circulating vitamin D levels before a prostate cancer diagnosis are linked to improved survival outcomes. Men at the higher end of the vitamin D range (75 nmol/L or higher) experienced roughly a 25% lower risk of dying from prostate cancer compared to those with the lowest levels. This association remained robust even after researchers adjusted for age, lifestyle, and clinical factors like tumor stage and grade. While this does not prove that supplements directly improve survival, it highlights a strong link between vitamin D status and disease resilience.​
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• Observational Study on Diet Quality and Frailty Risk
  ​A large prospective study following over 5,000 men found that a healthy diet after diagnosis significantly reduces the risk of aging with frailty. Men who followed eating patterns rich in vegetables, fruits, whole grains, and healthy fats had an 8–19% lower risk of developing symptoms like persistent fatigue and reduced strength. The benefit appeared to be independent of other health behaviors like exercise and smoking, reinforcing the specific role of diet quality in maintaining strength. Researchers suggest that tailoring dietary recommendations to emphasize plant-based foods and lean proteins can help survivors maintain long-term health and strength.​
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• Antibody MQI-201 for Targeting “Cold” Tumors
  MQI-201 is a fully human antibody designed to treat “cold” tumors, such as pancreatic and hormone-resistant prostate cancer, by targeting the TRPV6 calcium channel. TRPV6 is highly expressed on tumor cells but largely absent in normal healthy organs, providing a precise target. In preclinical models, MQI-201 reduced tumor size by 70% to 90% by disrupting calcium signaling and reprogramming the local immune landscape. The antibody not only stresses cancer cells directly but also increases the number of cytotoxic T cells and natural killer cells within the tumor environment.​
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• JZY-2233 PSMA-Targeted Degrader-Antibody Conjugate
  JZY-2233 is a targeted therapy that combines an anti-PSMA antibody with a potent CBP/p300 degrader payload. These proteins help the androgen receptor drive cancer growth, and JZY-2233 is designed to degrade them specifically within PSMA-positive tumor cells to avoid systemic toxicity. In laboratory studies, a single dose produced complete tumor suppression in LNCaP xenografts for more than 90 days. By restricting the degrader’s action to the tumor, the conjugate demonstrated a more favorable safety profile and a wider therapeutic window compared to unconjugated small-molecule degraders.​
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• XYA02-8-ADC Targeting MUC1-C in Resistant Prostate Cancer
  ​The antibody–drug conjugate XYA02-8-ADC targets the MUC1-C oncoprotein, which is overexpressed in aggressive castration-resistant and neuroendocrine variants of prostate cancer. MUC1-C helps these tumors survive even after hormone therapy by promoting stem-cell-like features. Preclinical animal models showed that this ADC achieved 70% tumor growth inhibition. Crucially, the treatment remained effective in both androgen-replete and androgen-depleted environments, suggesting it could provide a new option for patients who no longer respond to standard androgen receptor-targeted therapies.
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• The CNTF Pathway: How Exercise Protects the Prostate
  ​New preclinical research has uncovered a mechanism showing that exercise slows prostate cancer growth by activating a pathway involving the cytokine CNTF. Physical activity increases CNTF levels, which prevents tumor-supporting cells called fibroblasts from turning into aggressive, scar-producing myofibroblasts. This change creates a less supportive environment for the cancer and allows more CD8+ T cells to infiltrate and attack the tumor. Interestingly, giving sedentary mice a lab-made version of CNTF achieved similar anti-tumor effects and enhanced the efficacy of immunotherapy.​
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• Trispecific T-Cell Engager QLS2401 for Advanced Disease
  QLS2401 is a trispecific T-cell engager (TCE) designed to simultaneously bind PSMA and STEAP1 on prostate cancer cells and CD3 on T cells. By targeting two tumor antigens at once, QLS2401 aims to improve binding strength and reduce the risk of the cancer becoming resistant through the loss of a single target. Preclinical data show that the molecule induces potent tumor cell killing and is well tolerated in animal models, with a safety profile that compares favorably to other advanced T-cell engager platforms.​

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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