LAST WEEK TODAY!

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

Hi fellow warriors! Here we are again. We fall, we get back up, we gather our strength, and we move forward. Another week of encouraging news, my friends. 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 1 Trial: GLR2037 First-in-Human Study
  The GLR2037 investigational agent has entered early clinical development as a first-in-human study for patients with advanced prostate cancer. This drug is an androgen receptor (AR)–targeting proteolysis-targeting chimera (PROTAC), which is designed to promote the degradation of the AR rather than simply inhibiting it. By utilizing the ubiquitin-proteasome pathway, GLR2037 aims to bypass common resistance mechanisms, such as AR mutations and splice variants, that often limit the effectiveness of traditional inhibitors.​
  ​
• Phase 1 Trial: HITMAN-PC Results
  The HITMAN-PC trial investigated a metabolic approach to managing biochemical relapse by combining hydroxychloroquine (HCQ) and SUBA-itraconazole (SI) to disrupt lysosomal function and cholesterol trafficking. While the study reported that no patients achieved a PSA decline of 50% or greater, the regimen successfully stabilized the disease, resulting in a median PSA progression-free survival of 5.5 months. Furthermore, the time-to-ADT was 14.3 months, suggesting that this combination may help postpone the need for systemic hormone therapy in high-risk patients.​
  ​
• Phase 2 Trial: EQUIP Quality-of-Life Study
  The EQUIP trial is evaluating whether transdermal estrogen patches + ARSI can serve as an effective alternative to standard LHRH analogues + ARSI for achieving androgen suppression in men with metastatic hormone-sensitive prostate cancer. Because traditional hormone therapy drastically lowers estrogen levels, leading to side effects like hot flashes, fatigue, and impaired bone health, researchers are testing if restoring estrogen signaling via patches can maintain antitumor efficacy while improving overall well-being. The study is randomized, and it includes a crossover option for patients who experience refractory hot flashes while on standard-of-care therapy.​
  ​
• Phase 3 Trial: The ENHANCE Dose-Reduction Study
  The ENHANCE trial is a major UK-based study enrolling approximately 1,500 men to determine if reduced doses of common hormone therapy add-on drugs (abiraterone, enzalutamide, darolutamide or apalutamide) can fight cancer as effectively as full doses. The primary goal of this research is to slash the harsh side effects associated with these treatments, such as crushing fatigue and high blood pressure, while maintaining cancer control. Participants are randomized in a blinded setup to receive either the standard full dose or a reduced dose, with researchers tracking survival, PSA levels, and quality-of-life surveys.​
  ​
• Phase 3 Trial: Post-hoc Analysis of PSA Control in EMBARK
  A recent post-hoc analysis of the EMBARK trial suggests that durable, long-term PSA control can persist in a subset of patients even after their testosterone has recovered to normal levels. This analysis looked at men with high-risk biochemical recurrence who suspended therapy at week 37 after achieving deep PSA suppression; it found that approximately 3–4% of patients maintained a PSA below 0.2 ng/mL for years despite the restoration of physiologic androgen levels. These findings indicate that an intensive, finite course of hormonal therapy might induce a biologically meaningful “reset” or prolonged remission in selected individuals.​
  ​
• Blood Lipid Profiles as Metabolic Signatures A study published in Nature has demonstrated that plasma lipidomics can act as a non-invasive window into tumor metabolism and treatment response in patients with metastatic castration-resistant prostate cancer. The research found that men with this disease have a distinct lipid profile, which shifts noticeably when they begin treatment with enzalutamide. Specifically, the levels of a particular sphingomyelin, SM 18:1–18:1, were linked to better progression-free and overall survival, serving as a metabolic signature of a favorable response to therapy. These results suggest that monitoring blood fats could help clinicians identify early signs of treatment resistance.​
  ​

Preclinical Research & Reviews

• Amino Acid Enhancement for Nanoparticle Delivery
  Researchers have discovered that a cocktail of three amino acids, methionine, arginine, and serine,can significantly boost the effectiveness of lipid-nanoparticle (LNP) delivery for mRNA and CRISPR therapies. In animal models, co-administering these amino acids with LNPs increased mRNA expression by 5- to 20-fold across various delivery routes, including intravenous and intramuscular injections. Additionally, this mix improved CRISPR gene-editing efficiency in the lungs from roughly 25% to nearly 90%. This discovery suggests that improving cellular uptake through metabolic priming may be just as vital as redesigning the nanoparticles themselves.​
  ​
• Patient-Derived Organoids from TUR-P Samples
  Scientists have developed a low-cost method to grow patient-derived organoids using prostate tissue fragments that are normally discarded during routine TUR-P procedures. These “mini-tumors” accurately replicate the genetic alterations and androgen-receptor signaling found in the original patient’s cancer. Because the organoids’ responses to drugs in the lab often mirror the clinical outcomes seen in the actual patients, this platform has the potential to be used as a predictive tool for personalizing treatment strategies for men with advanced or treatment-resistant disease.​
  ​

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