A stress-adaptive lipid kinase axis defines metabolic vulnerabilities in neuroendocrine prostate cancer

Simultaneous inhibition of the lipid kinase PIKfyve and fatty acid synthase (FASN) triggers a terminal unfolded protein response and apoptosis in neuroendocrine prostate cancer cells, removing their ability to tolerate endoplasmic reticulum stress. The authors show that cells of this subtype maintain lysosomal homeostasis through a PIKfyve–ER stress–SREBP lipogenesis axis, making it a therapeutic target. Combined inhibition of both proteins suppressed tumour growth in preclinical models. This is laboratory work in cells and animal models: neither agent was given to patients, and the summary does not reproduce numerical values.