LAST WEEK TODAY!

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

Hi fellow warriors! For biology discovery enthusiasts (and AI applications) like me, last week was really exciting! But we also have good news on the clinical trial front! 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

• AMPLITUDE Trial: Niraparib Combination Significantly Extends Progression-Free Survival in HRR-Altered mCSPC​
  The AMPLITUDE trial (NCT04497844) explored a combination of niraparib, a PARP-1/2 inhibitor, with abiraterone acetate (Akeega) and prednisone for men with metastatic castration-sensitive prostate cancerwho have HRR gene alterations. This double-blind trial involved 696 men with specific HRR gene alterations, including BRCA1, BRCA2, and others. The combination significantly extended progression-free survival, with the median not yet reached in the niraparib group versus 29.5 months in the control arm, marking a 37% reduction in the risk of disease progression or death. The benefit was particularly notable in patients with BRCA1 or BRCA2 mutations. Additionally, the treatment significantly delayed the onset of cancer-related symptoms. While overall survival data are still maturing, early trends appear favorable but are not yet statistically significant. Safety data showed a manageable profile.
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• Phase 1 XL309: A Novel USP1 Inhibitor for BRCA1/2-Mutated Solid Tumors, Including mCRPC​
  XL309 is currently in a Phase 1 first-in-human trial for BRCA1/2 mutated solid tumors, including metastatic castration-resistant prostate cancer. This novel cancer drug candidate is a potent and selective inhibitor of ubiquitin-specific protease 1 (USP1), an enzyme crucial for DNA repair.The strategy aims to potentially synergize with existing PARP inhibitorsor overcome their resistance. Preclinical studies confirmed XL309’s potency and showed robust antitumor activity, particularly in BRCA1/2-mutant tumors. When combined with PARP inhibitors or irinotecan, XL309 produced durable tumor regressions, indicating strong synergy. XL309 is now being tested as both monotherapy and in combination with olaparib in patients with advanced BRCA-mutated solid tumors.
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• ACE-232 Update: Phase 1 Trial Initiated for Novel Oral CYP11A1 Inhibitor in mCRPC​
  ACE-232 is a novel oral CYP11A1 inhibitor designed to treat metastatic castration-resistant prostate cancer. This first-in-human study, conducted in the U.S. and China, aims to assess its safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy to determine a recommended Phase II dose. Preclinical data suggest ACE-232 offers a superior profile compared to earlier CYP11A1 inhibitors (Opevesostat/ODM-208), with potent activity, a favorable pharmacokinetic profile, and excellent tolerability. The drug functions by selectively inhibiting CYP11A1, an enzyme vital for adrenal steroid hormone synthesis, thereby suppressing androgen production in treatment-resistant prostate cancer.

Preclinical Research

• New Research Reveals Aspirin’s Immune-Boosting Mechanism Against Cancer Metastasis​
  A new study published in Nature in May 2025 suggests an additional mechanismby which aspirin may help combat cancer. The study found that aspirin reduced cancer spread in mice by enabling immune cells, specifically T cells, to attack spreading cancer cells. This occurs because aspirin blocks an enzyme (COX-1) in platelets, which stops the production of TXA2, a molecule that normally weakens T cells. With less TXA2, T cells remain strong and effective.Human studies also showed aspirin users had a lower risk of metastasis (64% less likely) and fewer cancer deaths (49% less likely) in early-stage cases. These findings suggest aspirin’s potential in preventing cancer spread, particularly in early-stage cases.
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• Zebrafish Embryo MicroRNAs Offer a Novel Approach to Inhibit Cancer Spread​
  Italian researchers have found that microRNAs (miRNAs) derived from zebrafish embryos can slow down the spread of aggressive breast cancer, a discovery published in the International Journal of Molecular Sciences in 2025. This suggests a new approach to make cancer cells less harmful by changing their behavior. The study revealed that these zebrafish molecules, particularly miR-218-5p, act as a “brake” on the PI3K pathway, a common driver of cancer cell proliferation and migration. This action causes cancer cells to stop forming structures that aid movement and instead begin sticking together like normal cells, forming tissue-like structures (basically, tumor reversion). In breast cancer cells, this treatment led to a 78% reduction in movement and 45–55% reduction in invasion.
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• AI-Engineered Dynamic Proteins: A Pivotal Advancement with Broad Implications​
  Researchers at UCSF have achieved a significant breakthrough by engineering an artificial protein capable of dynamic movement and shape-shifting, a behavior previously exclusive to natural proteins. This advancement, published in Science, represents a pivotal shift from static to dynamic protein design. The implications for cancer research are vast. These dynamic synthetic proteins could lead to biosensors that detect disease markers or therapeutics that activate only under precise conditions within the body. Such “smart proteins” might identify tumor-specific environments, selectively respond to cancerous cells while sparing healthy tissue, or deliver drugs directly to malignant cells, enhancing precision and reducing side effects. This achievement highlights the transformative potential of integrating artificial intelligence with molecular biology, laying the groundwork for a new era in synthetic biology and cancer treatment.
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And…that’s all folks! For today at least!
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Have a great weekend!

Max