LAST WEEK TODAY!

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

Hi fellow warriors! Here I am again! I think research is still a bit on holiday in terms of the number of studies, but the quality of the trials expected to start in 2026 looks very high. Let’s take a look at them together. 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: PT-112 for End-Stage Prostate Cancer​
  PT-112 is a novel platinum-based therapy that features a pyrophosphate structure designed to allowit to accumulate in bone tissue while also penetrating soft tissue. Unlike traditional platinums, it triggers immunogenic cell death through ribosomal inhibition rather than DNA crosslinking, which may activate immune responses in patients whose cancer no longer responds to androgen receptor (AR) signaling. Following a successful Phase 2 dose-finding study, the FDA cleared PT-112 for a pivotal Phase 3 trial in mid-2025. Results of the Phase 2 trial showed significant clinical activity, including high rates of circulating tumor cell (CTC) conversion to zero and notable declines in alkaline phosphatase associated with pain relief.​
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• ADI-212: Engineered Gamma Delta T Cells​
  ADI-212 is a new immune cell therapy that utilizes gamma delta T cells engineered to target PSMA-positive metastatic prostate cancer. These cells are modified with a special version of IL-12 that only activates when the cells encounter PSMA on cancer cells, helping to reshape the tumor environment and awaken other immune cells. Additionally, researchers used CRISPR gene editing to remove MED12, a protein that normally limits T cell growth, resulting in cells that multiply faster and remain active longer. In laboratory tests, ADI-212 successfully killed prostate cancer cells over six rounds of attack without showing signs of exhaustion. Animal models treated with a single injection experienced complete tumor shrinkage and lasting protection against new tumor growth. Clinical testing for this therapy is scheduled to begin in the first half of 2026.​
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• Phase Ib/II Trial: BrUOG360 (Copanlisib Plus Rucaparib)​
  The BrUOG360 clinical trial investigated the combination of copanlisib (a PI3K inhibitor) and rucaparib (a PARP inhibitor) in patients with mCRPC. This approach is based on preclinical models suggesting that PI3K inhibitors can sensitize tumors to PARP inhibitors by disrupting alternative DNA repair pathways. The trial focused on patients with homologous recombination deficiency (HRD), a group that represents about 4% of mCRPC cases where concurrent PI3K alterations often occur. Preliminary efficacy data from the Phase II portion revealed a PSA50 response rate of 23%, with one patient maintaining stable disease despite having been previously exposed to PARP inhibitors. Additionally, mechanistic studies suggest that this dual inhibition may enhance T-cell infiltration into the tumor environment.​

Preclinical Research & Reviews

• Sapu-003 (Deciparticle Everolimus)​
  Sapu-003 is a nanoparticle-formulated version of everolimus that has recently received approval for first-in-human Phase 1 testing in breast cancer.Utilizing the “Deciparticle” delivery platform, this intravenous formulation achieves 80-100% systemic absorption, significantly outperforming the 10-20% bioavailability of standard oral tablets. This delivery method also reduces gastrointestinal drug accumulation by over 60% while improving tumor penetration in preclinical models. The therapy targets the mTORC1 kinase, which becomes hyperactive in up to 50% of prostate cancer cases following PTEN loss or androgen deprivation therapy. This platform holds particular promise for neuroendocrine prostate cancer (NEPC), an aggressive, AR-independent subtype that has shown biochemical response rates of 70-75% in retrospective proof-of-concept studies using everolimus. The upcoming clinical trial aims to establish the optimal dosing and safety profile for humans by later in 2026.​
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• PSMA-1-DOTA: Targeted Radioligand Therapy​
  PSMA-1-DOTA is a novel ligand developed to enhance the precision of PSMA-targeted radioligand therapy (RLT) while minimizing common side effects like salivary gland damage. In preclinical evaluations, this ligand demonstrated a binding affinity to PSMA that is four times greater than existing established ligands. Imaging in mouse models revealed that PSMA-1-DOTA has markedly lower uptake in salivary glands, lacrimal glands, and kidneys, reducing the risk of debilitating dry mouth and toxicity. Therapeutic tests confirmed that it provides tumor growth inhibition equivalent to standard treatments like Pluvicto. Validation in a human compassionate-use PET scan further confirmed strong tumor targeting with minimal off-target accumulation.​
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• Dual FOXA1/FOXA2 Targeting for Lineage Plasticity​
  New research focuses on targeting FOXA1 and FOXA2, pioneer transcription factors that control the “identity” of prostate cancer cells and their ability to survive. While FOXA1 is critical for hormone-sensitive growth, FOXA2 enables the cancer to escape treatment by driving neuroendocrine features and lineage plasticity in advanced stages. By blocking both factors through genetic or drug-based methods, the cancer’s growth network falls apart, preventing cells from switching between hormone-dependent and hormone-independent states. This dual targeting has proven effective in laboratory models at halting cell division and shutting down aggressive gene networks. Although these findings represent a significant shift toward targeting gene control hubs, the research is currently in the early preclinical stage.​

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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