LAST WEEK TODAY!

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

Hello fellow warriors! Please bear with me for one more week. Next Friday the annual AACR 2026 meeting begins, and I should finally have access to the clinical trial data that will be presented. It will be a very busy weekend!
For now, here’s this week’s newsletter, which is still very interesting. 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: TSL2109 Dual-Target Inhibition
  TSL2109 is an experimental oral drug currently being evaluated in a phase 1 clinical trial for patients with advanced solid tumors, specifically metastatic castration-resistant prostate cancer (mCRPC/APMR) and certain breast cancers. The drug is designed to simultaneously target CDK4/6 and DYRK2, blocking the signals that instruct cancer cells to divide. Preclinical data indicates that TSL2109 remains active even in tumors resistant to enzalutamide by increasing levels of the p53 protein, which helps stop the growth of damaged cells and interrupts backup pathways the cancer uses to escape treatment. The primary goal of the ongoing human study is to establish safety and optimal dosing while monitoring for early signs of antitumor activity.​
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• Phase 1 Trial: EXS74539 LSD1 Inhibitor
  EXS74539 (also known as REC-4539) is undergoing a phase 1 trial to determine the correct dosage for treating various solid tumors, including aggressive prostate cancer. The drug works by blocking LSD1, a protein that drives a deadly gene network and helps resistant tumors continue growing after hormone therapy fails. A unique feature of EXS74539 is its ability to cross the blood-brain barrier, which may help treat cancers that spread to the brain. Additionally, it is engineered to minimize blood-related side effects, such as low platelets, which have historically been an issue for other drugs in this class.​
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• Phase 2 Trial: Darolutamide Monotherapy (ARAMON)
  ​The ARAMON trial is a phase 2 study investigating the efficacy of using darolutamide alone for 52 weeks in men with biochemical recurrence of castration-sensitive prostate cancer (CSPC/APMS). Unlike standard androgen deprivation therapy (ADT), which suppresses testosterone to very low levels, darolutamide monotherapy allows testosterone levels to remain higher, potentially improving quality of life by avoiding side effects like hot flashes and bone loss. Results showed that 65% of patients achieved a PSA level of <0.2 ng/mL by week 52, suggesting that this approach can provide strong cancer control while remaining highly tolerable.​
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Preclinical Research & Reviews

• TB511 Peptide-Drug Conjugate for Immune Reprogramming
  ​Recent research identifies TB511 as a promising peptide-drug conjugate that targets M2 macrophages, immune cells that typically protect and feed tumors in castration-resistant prostate cancer. TB511 uses a targeting peptide called TAMpep to bind to CD18 on these specific macrophages and delivers a payload that destroys their mitochondria. In mouse models, removing these suppressive M2 cells flipped the tumor environment from “cold” to “hot,” reactivating T cells and Natural Killer (NK) cells to fight the cancer. This treatment not only reduced tumor size but also suppressed markers for metastasis and blood vessel formation.​
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• PCWG4 Updates to Advanced Prostate Cancer Terminology
  ​The Prostate Cancer Working Group 4 (PCWG4), published in 2026, has overhauled the terminology used in advanced prostate cancer trials to be more patient-centric and scientifically accurate. The update replaces terms like “castration-resistant” (CRPC) and “hormone-sensitive” (HSPC) with Androgen Pathway Modulation (APM) terminology, specifically APM-resistant (APMR) and APM-sensitive (APMS). Beyond language, the new guidelines integrate PSMA-PET imaging for staging and emphasize patient-reported outcomes (PROs) to better capture how treatments affect a patient’s daily life and symptoms.​
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• Scan Growth Without PSA Rise in Enzalutamide Treatment
  ​A post-hoc analysis of the ARCHES and PROSPER clinical trials has highlighted a phenomenon known as discordance, where prostate cancer shows visible growth on scans despite stable PSA levels. This occurred significantly more often in patients treated with enzalutamide than in those on ADT alone, with over 20% of progressing patients in the PROSPER trial showing no PSA rise. Because patients experiencing this hidden progression tend to have worse overall survival and a higher incidence of liver metastases, experts now recommend routine imaging (CT or MRI) alongside blood tests to ensure cancer growth is caught early.​

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