Targeting AXL inhibits the growth and metastasis of prostate cancer in bone
We evaluated soluble AXL (sAXL or batiraxcept), a decoy receptor that can potently inhibit AXL signaling, as a single agent or in combination with docetaxel or carboplatin to treat prostate cancer (PCa) bone metastases. We used intratibial injection of multiple patient-derived xenografts with different characteristics, reflecting a traditional phase II clinical trial without pre-selection for a particular tumor characteristic. Inhibition of tyrosine kinase receptor AXL was highly effective as a single agent and showed additive effects when combined with docetaxel or carboplatin in suppressing PCa tumor growth in the bone and in suppressing metastasis to the lung. AXL inhibition suppressed critical cancer stem cell gene expression and significantly decreased proliferation and metastasis through suppression of E2F1 and NuSAP1. Our findings provide compelling preclinical data for testing batiraxcept in patients with prostate cancer with bone metastases. Overall design: To understand the mechanisms by which AXL inhibition suppressed mPCa AC and NEPC in the bone microenvironment, we profiled the transcriptomes of LuCaP PDX bone tumors with or without sAXL treatment alone or combination with docetaxel or carboplatin by RNAseq.