LAST WEEK TODAY!

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

Hi fellow warriors! Holidays are in the air, but we still have something new for you this week! 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 Clinical Trial for Sn-117m-DTPA​
  Sn-117m-DTPA, also known as Pentetate stannic Sn-117m, is an emerging radiopharmaceutical that functions as a theranostic agent, combining diagnostic imaging and targeted radiotherapy. It is being studied for its potential to treat painful bone metastases, particularly in patients with metastatic castration-resistant prostate cancer (mCRPC). The chelating agent DTPA directs the radioactive tin isotope (Sn-117m) to specific areas in the body. Its gamma photon emission allows detection with standard gamma cameras to monitor its distribution and confirm uptake in bone lesions. When localized in bone, Sn-117m-DTPA emits low-energy conversion electrons and Auger electrons, which have a short tissue penetration range (0.2–0.3 mm), concentrating radiation locally. This mechanism may reduce radiation exposure to surrounding tissues, including the bone marrow, and has been associated with low rates of myelotoxicity/minimal bone marrow toxicity in early studies. The research aims to develop Sn-117m-DTPA from a palliative agent into one that can actively fight metastases.
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• OncoACP3 Moving from Imaging to Treatment Option​
  OncoACP3 is a novel prostate cancer therapy in early clinical development, notable for being a small-molecule ligand that targets acid phosphatase 3 (ACP3), an enzyme highly expressed in prostate cancer cells. This agent holds a dual role as both a diagnostic PET imaging agent and a therapeutic. Preliminary Phase 1 data from its use as a PET imaging agent showed selective uptake in prostate tumors and sustained retention over time, with minimal accumulation in healthy tissues.Encouraged by these findings, developers are preparing to initiate a clinical trial to investigate OncoACP3 as a targeted radiotherapeutic. A key feature is its compatibility with alpha-emitting radioisotopes like actinium-225, which deliver more potent, localized energy with reduced damage to surrounding healthy tissue compared to beta particles.
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• Phase 1/2 Clinical Trial for ATRN-119 a New ATR Inhibitor​
  ATRN-119 is a new investigational cancer drug, currently in early-stage clinical trials, that is showing promise as an ATR inhibitor. It is designed to disrupt cancer cells’ ability to survive DNA damage. This drug is particularly effective for tumors with mutations in DNA repair genes, especially those with ATM loss-of-function. Its macrocyclic structure provides high selectivity for ATR. Cancer cells with ATM mutations are dependent on ATR, and blocking it can lead to lethal DNA damage through a concept known as synthetic lethality. In early trials, three patients receiving ATRN-119 as a monotherapy at 550 mg twice daily experienced tumor shrinkage of 7%, 14%, and 21% before reaching the expected Phase 2 dose. A significant improvement over other drugs in its class, ATRN-119 has shown minimal hematological toxicity, which could enable continuous dosing and makes it a strong candidate for combination therapies, such as with PARP inhibitors.

Preclinical Research

• Cholesterol Makes Cancer Cells Resistant to Hyperthermia​
  Scientists at Chiba University in Japan have discovered that cholesterol helps certain cancer cells survive high temperatures, providing insight into why some tumors resist heat-based therapies like hyperthermia. Hyperthermia involves heating tumors to about 50°C to kill cancer cells and activate the immune system, making it a potential companion to immunotherapy. Heat-resistant cancer cells contain significantly more cholesterol in their membranes than heat-sensitive ones, where this extra cholesterol acts as a shield to prevent membrane fluidity and physical damage from heat stress. Experiments with cholesterol-depleting drugs in lab-grown cells and mice with implanted tumors demonstrated that reducing cholesterol made cancer cells far more vulnerable to heat. The combination of cholesterol-lowering drugs and targeted heat treatment resulted in dramatic shrinkage and often total disappearance of tumors in mouse models, outperforming heat treatment alone. These findings suggest that measuring cholesterol levels in tumors could help predict which patients would benefit most from hyperthermia, and that this combination approach could improve hyperthermia’s effectiveness and potentially boost cancer immunotherapies by triggering immune-stimulating necrosis.
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And…that’s all folks! For today at least!
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Have a great weekend!

Max