LAST WEEK TODAY!

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

Hi fellow warriors! Here I am again! This week I had little time to post in the community, but there are still some interesting updates on the website! 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.
​For more details on everything I talk about here, you can always visit ProstateWarriors.com.​

Clinical Research

• Phase 3 Trial: Opevesostat (MK-5684-004) as a CYP11A1 Inhibitor for mCRPC
  ​The MK-5684-004 Phase 3 trial is evaluating opevesostat, a first-in-class CYP11A1 inhibitor designed to block the initial step of steroid hormone production. By eliminating all ligands that activate mutant androgen receptors, the drug aims to treat patients with metastatic castration-resistant prostate cancer (mCRPC) who have progressed on prior next-generation hormonal agents (NHAs). Data from earlier Phase 1/2 trials demonstrated significant PSA50 responses (73.7%) specifically in patients with AR-LBD mutations, compared to only 8.7% in those with wildtype receptors. Pharmacodynamic results confirmed that the treatment effectively suppressed multiple hormones, including testosterone, which became undetectable in 87% of patients within the first week.
  ​More info here.​
  ​
• Phase 2 Trial: ARREST Trial and Precision Radiation Boosts
  ​The ARREST trial seeks to overcome the 50% failure rate of 177Lu-PSMA therapy by integrating targeted external beam radiation boosts. This hybrid approach addresses “cold spots” (metastatic lesions that do not absorb enough systemic radioligand to be destroyed), leading to skeletal complications like fractures and spinal cord compression. Using SPECT-CT and FDG-PET/PSMA scans, researchers identify high-risk or symptomatic “troublemaker” lesions for a single, high-precision radiation dose. Beyond direct killing, this radiation supercharges PSMA expression on cancer cells, resulting in an 18% protein increase and a 2.6-fold mRNA spike, which makes subsequent doses of 177Lu-PSMA more effective. Preclinical mouse studies supporting this trial showed that the combination could extend survival by 60% compared to radiation alone.
  ​More info here.​
  ​
• Docetaxel Rechallenge vs. Cabazitaxel: VA Cohort Study
  ​A retrospective cohort study involving 669 veterans compared the efficacy of docetaxel rechallenge against cabazitaxel in patients with mCRPC who had not progressed during their initial docetaxel treatment. The study found that docetaxel rechallenge resulted in a superior median overall survival of 12.3 months, compared to 9.6 months for those receiving cabazitaxel. Additionally, docetaxel rechallenge achieved a significantly higher PSA90 decline rate (9.8%) than cabazitaxel (3.0%). Despite these survival and response advantages, the time on treatment remained similar between the two groups, and both cohorts had comparable subsequent use of other therapies like immunotherapy or PARP inhibitors. The findings suggest that for specific patients without prior docetaxel progression, rechallenging with the same drug may be more effective than switching to cabazitaxel.
  ​More info here.​
  ​

Preclinical Research & Reviews

• Discovery of tRNA Halves Fueling Prostate Cancer Growth
  ​Research published in PLOS Biology has identified that tiny genetic fragments known as tRNA halves act as a catalyst for prostate cancer growth by disabling the cell’s natural “brakes”. In healthy cells, the p21 protein functions to pause cell division; however, in hormone-driven prostate cancer, tRNA halves latch onto the Y-box binding protein 1, which normally protects the mRNA blueprint for p21. Without this protection, the p21 blueprint degrades, allowing cancer cells to multiply rapidly and unchecked. Because these tRNA halves are over 140 times more abundant than the p21 blueprint, they easily overwhelm the cell’s protective mechanisms. Experimental removal of these molecules resulted in a sharp drop in tumor cell numbers, suggesting that targeting tRNA halves could be a new strategy for restoring the p21 brake and slowing tumor progression.
  ​More info here.​
  ​
• The ALCO5 Platform for Smart Antibody-Drug Conjugates
  ​The ALCO5 platform represents a technological advancement in creating “smart” cancer medicines by refining how antibodies are linked to powerful drug payloads. In these antibody-drug conjugates (ADCs), the antibody acts as a guided missile to find cancer cell markers, while the ALCO5 linker connects it to a wide variety of drugs, including those containing alcohol (–OH) groups that were previously difficult to use. This linker is designed to remain stable in the bloodstream to prevent off-target toxicity but releases the drug precisely once inside the cancer cell. Preclinical tests with ten different compounds showed that the platform maintains high drug potency while widening the therapeutic window, allowing for the delivery of harsh drugs over longer periods. Furthermore, the platform’s ability to carry a uniform number of drug molecules makes its behavior in the body more predictable than older linker systems.
  ​More info here.​

​

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.

If this newsletter was delivered to your SPAM folder, make sure to let your email system know that it is not spam.
​
​
Have a great weekend!

Max