LAST WEEK TODAY!

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

Here I am with the fourth newsletter from the site. In the next days I will be reporting some (hopefully) good news from an immune oncology symposium, fingers crossed!
Some of the subscribers suggested me to reactivate the donations button, do you think I should? Or maybe create a GoFundMe campaign? I cannot make too much noise or I would risk to kill my mother (age 95, self-sufficient).

We also have a podcast if you prefer to listen to the newsletter, you can find it HERE.​

Clinical Research

• JANX007 Phase 1a dose escalation trial: This trial for metastatic castration-resistant prostate cancer (mCRPC) showed that JANX007 was well-tolerated and demonstrated substantial clinical activity. All 16 patients treated had at least a 50% decline in PSA levels, with 63% achieving at least a 90% decline and 31% at least a 99% decline. 75% of patients maintained PSA50 declines for at least 12 weeks, and 50% maintained PSA90 declines for at least 12 weeks. Of the 8 patients evaluable for tumor response, 50% achieved an objective response rate, including confirmed and unconfirmed partial responses. Side effects were generally mild and mostly limited to the first cycle of treatment. The maximum tolerable dose has not yet been reached.
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• STAMPEDE trial: This trial investigated the use of metformin, a diabetes drug, to reduce side effects of hormone therapy in men with advanced prostate cancer. The study involved 1,874 men with metastatic prostate cancer who did not have diabetes. After two years, men taking metformin gained only half as much weight as those receiving standard treatment alone and had lower blood sugar levels and lower levels of harmful circulating fats, including cholesterol. Fewer patients in the metformin group reported signs of metabolic syndrome. Individuals taking metformin had a 10% lower risk of dying and lived for around six months longer than those receiving standard treatment only.
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• BNT324/DB-1311 Phase 1/2a clinical trial: This trial for various advanced solid tumors, including castration-resistant prostate cancer (CRPC), showed that BNT324/DB-1311, an antibody-drug conjugate targeting B7-H3, demonstrated encouraging antitumor activity and a manageable safety profile. In patients with CRPC, the unconfirmed objective response rate was 28.0%, with a median progression-free survival of 7.2 months. The most common side effects were manageable. The FDA has granted BNT324/DB-1311 Fast Track designation for the treatment of advanced/unresectable or metastatic CRPC and Orphan Drug Designation for the treatment of advanced or metastatic esophageal squamous cell carcinoma.
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• Matching-Adjusted Indirect Comparison (MAIC) study: This study, published on Nature, compared the effectiveness of three PARP inhibitor combinations: talazoparib plus enzalutamide (TALA + ENZA), olaparib plus abiraterone acetate (OLAP + AAP), and niraparib plus abiraterone acetate (NIRA + AAP) for the treatment of mCRPC. The analysis showed that TALA + ENZA was superior in slowing down cancer progression compared to both OLAP + AAP and NIRA + AAP. TALA + ENZA also showed promising results in terms of PSA response compared to OLAP + AAP.

Preclinical Research

• APVO442: This preclinical bispecific antibody is designed for targeted prostate cancer treatment with reduced side effects. It works by binding to PSMA on prostate cancer cells and CD3 on T cells, bringing them in close proximity to enhance tumor cell killing. Preclinical studies have shown that APVO442 effectively targets tumor cells, enhances the immune response, and has potential for combination therapy.
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• Activating the protein GP130: Researchers found that activating, rather than blocking, the protein GP130 could be a new approach to treating aggressive forms of prostate cancer. Studies in mice and human tissue samples showed that activating GP130 slowed tumor growth and stimulated the immune system.
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• Copper deprivation: This strategy focuses on depriving cancer cells of copper, which they need for rapid proliferation. Researchers developed nanofibers that can remove copper from tumor cells, leading to cell death. In laboratory tests, over 85% of breast cancer cells died within 72 hours of treatment, while healthy cells were unaffected.
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• Coral-inspired bone graft substitute: Researchers have developed a 3D-printed bone graft substitute inspired by coral. Preclinical studies have shown that this material promotes rapid bone growth and integrates seamlessly with human bone, offering a potential solution for bone defects caused by tumors.
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• Inhibiting the sterol regulatory element-binding protein (SREBP) can re-establish sensitivity to docetaxel in prostate cancer: Research published in The American Journal of Pathology indicates that combining docetaxel and mifepristone significantly reduced cancer cell viability in docetaxel-resistant prostate cancer models.The study identified SREBF-1, a transcription factor involved in cholesterol and lipid biosynthesis, as a down-regulated target. This discovery suggests a potential clinical approach to improve prostate cancer therapies, particularly in drug-resistant cases.
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• HWE reaction for anti-cancer drug synthesis: Researchers improved the Horner–Wadsworth–Emmons (HWE) reaction to create conjugated carbonyl compounds, which are building blocks for pharmaceuticals. This new method is more efficient and selective for producing the desired form of the compound, making it suitable for synthesizing hynapene analogues, chemicals with anti-cancer potential.It’s important to note that preclinical research is conducted in laboratory settings or with animals, and further research and clinical trials are needed to determine the safety and effectiveness of these approaches in humans.

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