A recent preclinical study has shed light on the promising effects of batiraxcept (sAXL), a novel soluble AXL signaling inhibitor, in suppressing prostate cancer (PCa) bone metastases. The findings suggest that batiraxcept could play a significant role in improving outcomes for patients whose cancer has advanced beyond hormone therapies.

Researchers focused on advanced prostate cancers that had metastasized to the bone, as these cases are often fatal after conventional treatments fail. Using human prostate cancer bone metastases and patient-derived xenograft (PDX) models, they examined how batiraxcept influences tumor growth and metastasis. In these models, tumor-bearing mice received treatments with batiraxcept, docetaxel, carboplatin, or combinations of these therapies. Tumor progression was tracked via serum PSA levels and bioluminescence imaging, while lung metastasis was assessed using qPCR. Additionally, comprehensive molecular profiling identified key genetic and protein changes triggered by the treatments.

The results were striking. High AXL phosphorylation, a marker of aggressive disease, was found in the bone metastases and correlated with worse survival outcomes. However, batiraxcept treatment, either alone or in combination with chemotherapy, effectively suppressed tumor growth in the bone and reduced metastasis to the lungs. The treatment also downregulated cancer stemness genes and disrupted several crucial signaling pathways, such as PI3K, JAK, MAPK, and E2F1/NUSAP1, all of which contribute to the aggressiveness and spread of prostate cancer.

Beyond the study’s implications for prostate cancer, it’s notable that batiraxcept will be evaluated in a Phase 3 clinical trial for clear cell renal cell carcinoma (ccRCC). This adds another layer of potential significance, as a successful outcome in ccRCC could strengthen the case for expanding batiraxcept’s use in other hard-to-treat cancers, including metastatic prostate cancer.

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