LAST WEEK TODAY!

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

Hi fellow warriors!
​A quick note from me: our newsletter runs on Kit.com, which costs $290/year to keep going. If you enjoy these updates and would like to chip in to help cover the renewal, you can do so here, or send me a message if you want to use a different system. No pressure at all!
Apart from that, a news interesting week of news just ended. There are some strategic moves in the air I think. 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 1/2 Trial: Tulmimetostat + ARPI Combo for mHSPC
  The TulmiSTAR-02 study will evaluate tulmimetostat, also known as DZR123, which is a novel and selective inhibitor targeting the EZH2 pathway. This EZH2 pathway may potentially overcome resistance mechanisms to existing androgen deprivation treatments. The initial Phase I component will focus on determining the optimal dosing of tulmimetostat when combined with standard androgen receptor pathway inhibitors (ARPIs) such as darolutamide or abiraterone. Following dose optimization, the Phase II portion will randomize 203 men with metastatic hormone-sensitive prostate cancer (mHSPC) to receive either the combination (tulmimetostat plus darolutamide) or darolutamide alone, enabling a direct comparison against the current standard treatment.
  ​
• Phase I/II Trial: AZD6621: A T-Cell Therapy Targets Hidden Prostate Cancer Driver
  Clinical validation for the novel immunotherapy AZD6621 is currently underway through the ACTIVATED-4-PC trial, a comprehensive Phase I/II study evaluating the safety, tolerability, and efficacy of AZD6621 in men diagnosed with metastatic prostate cancer. AZD6621 is a bispecific antibody designed to harness the body’s immune system by creating a molecular bridge that guides specialized CD8+ T-cells, or “killer” cells, directly to cancer cells. The treatment targets STEAP2, a protein considered an ideal therapeutic target because it is abundantly expressed across all stages of prostate cancer while remaining largely absent from healthy tissues outside the prostate.
  ​Note:the same (big) company having at least 4 different trials involving STEAP2…my feeling is that this target is hot and that they must already know that it has huge potential. Just my gut feeling!

Preclinical Research & Reviews

• PH1: Dual-Action Payload Targeting AR-V7 Resistance​
  The novel molecule PH1 is being investigated in preclinical models for its innovative approach in addressing a major hurdle in advanced prostate cancer: resistance driven by the androgen receptor splice variant 7 (AR-V7). Preclinical studies using the 22Rv1 metastatic castration-resistant prostate cancer (mCRPC) model show that PH1 is capable of potently reducing AR-V7 receptor expression, a result that existing ARPIs, including enzalutamide and apalutamide, cannot achieve. PH1 displays efficacy as a single agent in hormone-sensitive prostate cancer models and shows additive effects when combined with first-line ARPIs in the laboratory, suggesting potential utility both as first-line combination therapy and as a second-line option following ARPI resistance. Notably, once inside the cell, PH1 disrupts spliceosome function, leading to cancer cell death while simultaneously producing neoantigens that stimulate the immune system, a dual mechanism that may enhance the efficacy and durability of immune checkpoint therapies.
  ​
• A Hidden Brake: SCG2-LILRB4 Pathway Reprograms Immune Cells​
  Research published in Nature Immunology details a sophisticated molecular mechanism utilized by tumors to evade immune attack, identifying a pathway involving the hormone secretogranin 2 (SCG2). Scientists at UT Southwestern Medical Center found that when tumors produce SCG2, the hormone binds to the LILRB4 receptor found on myeloid cells, which are among the first immune responders to tumors. This binding triggers a cascade that fundamentally reprograms these myeloid cells from tumor fighters into immunosuppressive agents. The resulting activation of internal signaling pathways, including the recruitment of SHP proteins and independent activation of STAT3, transforms the myeloid cells, allowing them to prevent T cells from reaching and attacking the cancer. This discovery addresses a critical limitation in current immunotherapies, like checkpoint inhibitors, which benefit only 20 to 30 percent of cancer patients, as the SCG2-LILRB4 pathway represents an entirely different mechanism of immune evasion from known checkpoint pathways.
  ​

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 you 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