LAST WEEK TODAY!

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

Hi, fellow fighters! This week, the updates are primarily in preclinical research, but new guidelines for the use of SBRT are beginning to take shape, and they could be very exciting!

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

Clinical Research

• Metastasis-Directed Therapy (MDT): MDT, especially using stereotactic body radiotherapy (SBRT), is a changing approach in the treatment of metastatic prostate cancer. MDT offers ways to intensify treatment in aggressive cases and de-escalate therapy to minimize side effects, which can enhance patient quality of life.
  • The STOMP trial showed that MDT can delay the need for androgen deprivation therapy (ADT) in patients with oligometastatic hormone-sensitive prostate cancer (HSPC).
  • The ORIOLE trial demonstrated that SBRT improves progression-free survival in oligometastatic prostate cancer compared to observation alone.
  • The EXTEND trial found that adding MDT to intermittent hormone therapy improved outcomes in oligometastatic prostate cancer.
  • The ARTO trial showed that adding MDT to a new line of systemic therapy increased biochemical response rates and improved progression-free survival in oligoprogressive castration-resistant prostate cancer.
  • The PROLONG study showed that a comprehensive approach combining ADT, androgen receptor pathway inhibitors, and SBRT improved survival rates in patients with de novo low-volume HSPC.
  • The ARREST study demonstrated that SBRT-MDT is a safe and feasible option even for patients with polymetastatic disease.
• INKmune Immunotherapy Trial: A Phase I/II trial of the immune therapy INKmune for metastatic castration-resistant prostate cancer (mCRPC) has expanded to include U.S. military veterans. INKmune primes the body’s natural killer (NK) cells to better target and destroy tumor cells. The therapy is administered intravenously, and the trial is designed to evaluate safety and determine the most effective dose. The therapy may also be applicable to other NK-resistant tumors.
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• Aspirin and Prostate Cancer Recurrence: A study suggests that aspirin may help delay biochemical recurrence (BCR) in prostate cancer patients after robot-assisted radical prostatectomy (RARP), particularly in those with a high-risk ISUP grade of 4 or higher. The study found a meaningful increase in the 3-year BCR-free survival rate among aspirin users after statistical adjustments. Aspirin’s mechanism, which includes inhibiting cell proliferation and angiogenesis, likely contributes to these outcomes. However, the study’s retrospective nature and lack of data on dosage and duration call for further prospective trials.

Preclinical Research

• Batiraxcept and Bone Metastases: A preclinical study indicates that batiraxcept, a novel soluble AXL signaling inhibitor, effectively suppresses tumor growth in the bone and reduces metastasis to the lungs in advanced prostate cancer. High AXL phosphorylation was found in bone metastases and correlated with worse survival outcomes, but batiraxcept treatment, alone or with chemotherapy, downregulated cancer stemness genes and disrupted signaling pathways that contribute to the spread of prostate cancer. Batiraxcept is also being evaluated in a Phase 3 clinical trial for clear cell renal cell carcinoma (ccRCC).
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• WNT9B Gene Mutation: A mutation in the WNT9B gene has been identified as significantly increasing the risk of prostate cancer in men with a family history of the disease. The increased risk associated with the mutation ranged from two- to twelve-fold. This discovery adds WNT9B to the list of established high-risk prostate cancer genes.
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• EcDNA and Treatment Resistance: Research has revealed that extrachromosomal DNA (EcDNA) contributes to androgen receptor (AR) overexpression, genomic disorganization, and therapy resistance in metastatic castration-resistant prostate cancer (mCRPC). The AR gene can be present on circularized DNA outside the chromosome, leading to higher AR copy numbers and expression, which fuels tumor growth and reduces the effectiveness of standard treatments. This finding highlights the need for new therapeutic strategies.
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• Hydrogel Cancer Vaccines: A novel delivery system using lipopeptide hydrogels (LPHs) may significantly boost the effectiveness of peptide-based cancer vaccines. The LPH system acts as a depot for the sustained release of cancer-targeting peptides and enhances the immune system’s response. While initially focused on hepatocellular carcinoma (HCC), the technology holds promise for prostate cancer if tailored to prostate cancer-associated peptides.
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And…that’s all folks! For today at least!
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Have a great weekend!

Max