Prostate cancer metastasizes preferentially to bone leading to painful, bone destructive lesions and malignant disease progression for which there is no cure. The complexity and heterogeneity of prostate cancer bone metastases make them extremely challenging to treat and new therapies are urgently needed. We developed new patient-derived xenograft (PDX) models using surgical patient prostate cancer bone metastases which were implanted into immunodeficient mice. The resulting xenograft tumors replicated the tumor heterogeneity and bone lesions seen in patients. We are using our patient-derived xenograft models and prostate cancer cell line models to determine the mechanism of action of a new therapeutic target: the WNT5A/ROR1 signaling pathway in prostate cancer for which a therapeutic ROR1 inhibitor antibody, Cirmtuzumab, has been developed and clinically tested in CLL and metastatic breast cancer patients.