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Updated: May 30, 2025
06:32
Intra-Cardiac Injection of Human Prostate Cancer Cells to Create a Bone Metastasis Xenograft Mouse Model
Published on: November 4, 2022
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Targeting AXL Inhibits the Growth and Metastasis of Prostate Cancer in Bone
Chun-Lung Chiu1, Dalin Zhang1, Hongjuan Zhao1
1Department of Urology, Stanford University School of Medicine, Stanford, California.
Summary
A novel soluble AXL inhibitor, batiraxcept, effectively reduced prostate cancer bone metastasis growth and spread. This agent shows promise alone or combined with docetaxel or carboplatin for treating lethal metastatic prostate cancer.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- Castration-resistant and neuroendocrine prostate cancer with bone metastasis is lethal, with limited treatment options beyond docetaxel and carboplatin.
- There is an urgent need for novel agents that target key pathways in prostate cancer and can synergize with existing therapies to inhibit bone metastasis.
Purpose of the Study:
- To assess the expression of phosphorylated AXL in human prostate cancer bone metastases.
- To evaluate the efficacy of a novel soluble AXL signaling inhibitor, batiraxcept, in combination with docetaxel or carboplatin against prostate cancer bone metastasis and lung metastasis.
Main Methods:
- Immunohistochemistry (IHC) was used to assess phosphorylated AXL expression.
- Patient-derived xenograft models of prostate cancer bone metastasis were treated with batiraxcept, docetaxel, or carboplatin, alone or in combination.
- Tumor growth, burden, and lung metastasis were quantified using serum PSA, bioluminescence, Ku70 staining, and qPCR. Transcriptomic and proteomic analyses were performed.
Main Results:
- High AXL phosphorylation in bone metastases correlated with poorer survival.
- Batiraxcept, alone or with docetaxel/carboplatin, significantly inhibited tumor growth and lung metastasis.
- Mechanisms included repression of cancer stemness genes and key signaling pathways (PI3K, JAK, MAPK, E2F1/NUSAP1).
Conclusions:
- Batiraxcept demonstrates significant preclinical efficacy against prostate cancer bone metastasis.
- The study provides a strong rationale for batiraxcept's use as a single agent or in combination therapy for lethal metastatic prostate cancer.
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