New understanding of how prostate cancer adapts to the stress of androgen receptor targeted drugs and becomes castrate-resistant, points to a lesser-studied family of lipid kinases as playing a pivotal role in this process. The findings indicate that specific inhibition of one isoform of these phosphatidylinositol-5-phosphate-4-kinases (PI5P4K) could provide a route to prevent cancer cells altering their metabolism and becoming resistant to androgen deprivation.