The study provides proof of concept that dysregulated or aberrantly expressed HSD17B2, HSD17B3, SHBG, and SRD5A1 drive enhanced dissemination, phenoconversion, and therapy response of aggressive metastatic, treatment-resistant (platinum-based chemotherapy, ADT and/or immunotherapy) unresectable/advanced or recurrent PCa cells. The gene discussed is SHBG; the disease is posterior cortical atrophy.