LAST WEEK TODAY!

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

Hello fellow warriors! Summer is over, research publishing has picked up again, and this week we have plenty of interesting information to read! 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 1 Trial: SNV1521 PARP1 Inhibitor in mCRPC
  ​SNV1521 is an oral, next-generation PARP inhibitor engineered to selectively target PARP1 while largely sparing PARP2, a design intended to minimize haematological toxicities such as anaemia commonly associated with dual inhibition. Interim results from an ongoing Phase 1 trial across advanced solid tumors, including metastatic castration-resistant prostate cancer (mCRPC), demonstrated good PARP inhibition, with manageable grade 1–2 adverse events and no dose-limiting toxicities. Initial clinical activity includes PSA responses in prostate cancer patients harboring BRCA2 alterations, and further patient recruitment is continuing.
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• Phase 1 Trial: JANX007 Plus JANX013 Combination Strategy in mCRPC
  ​A newly registered Phase 1 clinical trial is evaluating a novel two-signal immunotherapeutic approach combining JANX007 and JANX013 in up to 110 men with mCRPC. JANX007 is a tumor-activated PSMA×CD3 T-cell engager providing Signal 1 to recruit T cells to prostate cancer cells, whereas JANX013 is a PSMA×CD28 tumor-activated immunomodulator delivering Signal 2 to promote sustained T-cell activation and proliferation while minimizing systemic toxicity. Preclinical evidence demonstrates that adding CD28 co-stimulation substantially enhances tumor-cell killing and maintains T-cell effectiveness upon repeated challenge.​
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• Phase 1 Trial: ICP-B381 Bispecific Antibody-Drug Conjugate for mCRPC
  ​Following clearance of its Investigational New Drug (IND) application in China and planned filing in the United States, ICP-B381 is advancing into a Phase 1 human trial for solid tumors including mCRPC. ICP-B381 is a dual-targeting bispecific antibody-drug conjugate (ADC) designed to target both PSMA and STEAP1 simultaneously. In preclinical 22Rv1 prostate cancer models with low target expression, ICP-B381 achieved approximately 94% tumor-growth inhibition at 1 mg/kg, demonstrating superior efficacy compared to single-target PSMA or STEAP1 ADCs without causing treatment-related weight loss.
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• Phase 1/2 Trial: Tracking Response and Resistance to Lu-177 Plus Immunotherapy
  ​A post-hoc biomarker analysis of the PRINCE Phase 1/2 trial, which evaluated 177Lu-PSMA-617 combined with pembrolizumab in 37 men with mCRPC, investigated factors governing therapeutic response and resistance. Patients exhibiting low baseline ctDNA levels and high PSMA PET uptake experienced deeper and more durable responses, whereas treatment progression was marked by target PSMA loss and clonal expansion of tumor-suppressor gene alterations in TP53, RB1, or PTEN. These findings indicate that integrating liquid biopsies with PSMA and FDG PET imaging can help identify optimal candidates and track emerging resistance patterns.
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• Clinical Trial: Radium-223 Impact on Immune Activity in Bone Metastases
  ​A prospective clinical study involving 28 men with mCRPC and predominantly bone metastases evaluated whether Radium-223 therapy could induce immunogenic changes to enhance sensitivity to PD-1/PD-L1 checkpoint inhibitors.Contrary to preclinical expectations, serial 89Zr-atezolizumab PET imaging demonstrated a 64% reduction in median PD-L1 uptake in PSMA-positive bone metastases following three cycles of Radium-223. Additionally, lymphocyte levels in blood and tumor tissue declined, challenging the hypothesis that Radium-223 primes prostate cancer bone lesions for subsequent immunotherapy.
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• Clinical Study: 10-Year Outcomes of PET-Guided Radiotherapy for Recurrent Prostate Cancer
  ​A retrospective clinical study tracking 93 men with hormone-sensitive nodal recurrent prostate cancer over a median follow-up of 10 years evaluated PET-directed elective nodal radiotherapy combined with temporary androgen deprivation therapy (ADT). Results showed a 5-year overall survival of 95% and a 10-year overall survival of 77%, with 55% of patients remaining free from castration-resistant disease at a decade. Furthermore, 35% of patients remained free from any additional treatment at 10 years, demonstrating that targeted salvage nodal radiation with finite ADT can yield long-term disease control.
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• Clinical Study: Pre-Treatment ctDNA Blood Testing for High-Risk mHSPC
  ​A prospective observational study of 85 men with metastatic hormone-sensitive prostate cancer (mHSPC) investigated the prognostic utility of pre-treatment circulating tumor DNA (ctDNA) prior to initiating ADT.Detectable ctDNA was present in 64% of evaluable patients and was strongly associated with high disease volume, a 3.43-times higher risk of progression to castration resistance, and significantly shorter median overall survival (33 months vs. not reached). These results suggest ctDNA blood testing can complement standard imaging and PSA to risk-stratify patients before treatment begins.
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• Clinical Study: CEA as an Independent Prognostic Marker for Lu-177 PSMA Therapy
  ​An observational clinical study evaluated carcinoembryonic antigen (CEA) levels in patients undergoing 177Lu-PSMA therapy, identifying elevated baseline CEA as an independent marker for poorer progression-free and overall survival. Although CEA levels were biologically independent of PSA, combining CEA and PSA assessment improved risk stratification, potentially identifying an aggressive disease phenotype distinct from conventional neuroendocrine variants or PSMA PET disease extent.
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• Clinical Study: PSMA Retention in Suspected Neuroendocrine Prostate Cancer
  ​A retrospective clinical study evaluated eight men with mCRPC suspected of treatment-emergent neuroendocrine differentiation who underwent consecutive 68Ga-PSMA and 68Ga-DOTATATE PET/CT imaging. Surprisingly, PSMA expression persisted across all patients, displaying uptake equal to or greater than DOTATATE across all lesions, including liver, lung, bone, and lymph node metastases. These findings suggest that PSMA-targeted therapies should not be automatically ruled out when neuroendocrine transformation is clinically suspected without prior molecular imaging.​
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Preclinical Research & Reviews

• STEAP1 ADC Turning Tumour Killing Into an Immune Response
  ​Preclinical studies tested a STEAP1-targeted antibody-drug conjugate called vandortuzumab with different chemotherapy payloads.The versions carrying exatecan or DXd performed better than the MMAE version. They not only killed STEAP1-positive cancer cells, but also helped immune cells recognise and attack the tumour, activated T cells, and killed nearby cancer cells with little or no STEAP1. In mouse models, this led to strong and lasting tumour shrinkage. The treatment also appeared to train the immune system to recognise additional tumour targets, allowing it to attack even cancer cells that did not express STEAP1.
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• Targeted Protein Degradation for Undruggable Cancer Drivers
  ​Preclinical research exploring targeted protein degradation aims to eliminate previously “undruggable” oncogenic proteins in prostate cancer that lack traditional small-molecule binding pockets. In vivo animal studies confirmed that a novel targeted degrader successfully depleted its target protein across multiple tissues while maintaining favorable tolerability. This strategy demonstrates the potential of making cancer cells selectively destroy driver proteins rather than attempting to inhibit them.​
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• PSMA-Targeted Nanoparticles for CRISPR Genome Editing
  ​Preclinical research is exploring ways to use PSMA-targeting aptamers to carry CRISPR gene-editing tools directly into prostate cancer cells. Once inside the cell, CRISPR could potentially switch off cancer-driving genes, restore genes that normally suppress tumour growth, or interfere with pathways that allow the cancer to resist treatment. Researchers are also considering delivery systems that target more than one marker, such as PSMA and STEAP1, so the treatment could still reach tumour cells even when they do not all express the same target.
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• Tumour Microenvironment Reprogramming and AI-Powered DNA Decoding
  ​Recent research frontiers highlight two complementary advancements: animal experiments using targeted nanoparticles to reprogram “cold,” immunosuppressive tumor microenvironments, alongside Google DeepMind’s AlphaGenome Atlas. AlphaGenome Atlas utilizes AI to predict the functional impact of over nine billion single-letter DNA variants across coding and non-coding regions, offering prostate cancer researchers a powerful tool to identify genomic drivers and novel therapeutic targets.
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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