LAST WEEK TODAY!

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

Hello fellow warriors! Busy week for research, there are some promising news. 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 2 Trial: MRT-2359 and Apalutamide Combination
  ​This Phase 2 clinical trial is evaluating the investigational drug MRT-2359 in combination with apalutamide for patients with androgen receptor (AR) mutation-positive metastatic castration-resistant prostate cancer (mCRPC). The study, known as MODeFIRe-1, plans to enroll up to 25 patients who have previously shown disease progression on a second-generation AR inhibitor. MRT-2359 is a molecular glue degrader that targets GSPT1 to disrupt cancer-cell protein translation, while apalutamide acts complementarily by blocking AR signaling. The trial builds on an earlier Phase 1/2 combination study where a small subgroup of five patients with AR mutations all achieved PSA responses, including two with declines of at least 90%.
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• Phase 1 Trial: ADI-212 Off-the-Shelf CAR T Therapy for mCRPC
  ​The FDA has cleared the IND application to begin a first-in-human Phase 1 clinical trial evaluating ADI-212, a novel cell therapy for patients with metastatic castration-resistant prostate cancer, with enrollment anticipated to start in the fourth quarter of 2026. ADI-212 is an “off-the-shelf” (allogeneic) CAR T-cell therapy made from healthy donor cells and engineered to target prostate-specific membrane antigen (PSMA). Built on the tissue-resident Vδ1 subset of gamma delta T cells, ADI-212 is modified using CRISPR to knock out the MED12 gene to increase potency in solid tumors. Additionally, it carries membrane-tethered interleukin-12 (IL-12) to selectively boost localized immune attack power at the tumor site while minimizing toxic systemic side effects.
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• Phase 1 Trial: AK157D1 B7-H3–Targeted ADC in Advanced Prostate Cancer
  ​The investigational antibody-drug conjugate (ADC) AK157D1 has been cleared to enter a Phase 1 clinical trial for advanced solid tumors, offering a promising therapeutic pathway for advanced prostate cancer. This therapy targets B7-H3 (CD276), an aggressive surface protein that remains highly and stably expressed across primary, metastatic, castration-resistant, and neuroendocrine prostate cancer, making it a reliable target even when PSMA is downregulated. AK157D1 is constructed using a humanized IgG1κ antibody linked via a cleavable MC-AAA linker to a potent topoisomerase I inhibitor payload (DXd), and preclinical data suggest it may offer a reduced risk of hematologic toxicity and interstitial lung disease compared to older ADCs.
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• Clinical Trial: Daily Adaptive Radiotherapy After Prostate Surgery
  ​The DART-PHASER trial is a clinical study testing daily adaptive radiotherapy using artificial intelligence to adjust radiation plans in real time based on a patient’s daily anatomy. Early results from the first 42 patients, who received a shortened, intense schedule of 20 daily treatments, show that the AI-powered Ethos system significantly improves precision. The adapted plans covered the target area far more completely—delivering the intended dose to an average of 98.5% of the prostate bed compared to 92.1% for non-adapted plans—while simultaneously reducing the radiation dose to the rectum, which is expected to lower long-term bowel side effects. Because the average follow-up is currently short (14 months), the trial is continuing to enroll patients to verify long-term cancer control and late side effects. ​
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Preclinical Research & Reviews

• Circulating Tumor DNA (ctDNA) as an Early Compass for Metastatic Prostate Cancer
  ​While prostate-specific antigen (PSA) remains a crucial monitoring tool, it does not always capture the activity of treatment-resistant or neuroendocrine-like tumor clones. Circulating tumor DNA (ctDNA) can provide a more direct, earlier, and androgen-receptor-independent view of tumor burden, clonal evolution, and emerging resistance. A prospective study of 114 patients with metastatic castration-sensitive prostate cancer found that those with persistent ctDNA at cycles three or four of therapy had substantially worse overall survival than those whose ctDNA became undetectable, with a 24-month overall survival rate of 50% compared to 85%. Although ctDNA is a highly promising prognostic guide, randomized interventional trials are still required to prove whether changing treatment strategies based on ctDNA clearance actually improves patient survival.
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• BET and DNMT Inhibitor Combination for Treatment-Resistant Prostate Cancer
  ​Preclinical research from the University of Michigan suggests that combining BET inhibitors with DNMT inhibitors could establish a novel strategy for treating advanced, treatment-resistant prostate cancer. This work focuses on aggressive tumors that have undergone transdifferentiation to escape standard hormone therapies. In laboratory and mouse models, the combination of a BET inhibitor (which blocks gene-control proteins) and a DNMT inhibitor (which reverses gene-silencing changes) slowed tumor growth much more effectively than either drug alone. This combination also reversed many gene-activity changes associated with transdifferentiation and was well tolerated at low doses in mice, indicating it may partially push cancer cells out of their aggressive, adaptable state.
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• Targeting eIF4E to Reverse Lineage Plasticity and Restore Hormone Sensitivity
  ​Advanced prostate cancers frequently develop resistance through lineage plasticity, shifting from a hormone-dependent “luminal” state to a hormone-resistant “basal” state. Researchers discovered that the eIF4E cap-binding domain acts as a critical molecular control point that selectively boosts the translation of basal keratins which maintain this resistant state. By applying a novel drug, PF-07293623, to block eIF4E’s cap-binding site in AR-low cells and mouse models, they cut basal keratin production and successfully increased androgen receptor (AR) protein levels. When PF-07293623 was combined with standard enzalutamide therapy in mice, previously resistant basal tumors shrank, demonstrating that targeting eIF4E can “re-educate” resistant cancer cells to make them sensitive to hormone therapies once again.​

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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