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

PIKfyve overexpression in neuroendocrine prostate cancer creates a metabolic vulnerability that can be exploited by dual inhibition of PIKfyve and FASN.

• Why it matters: Understanding how NEPC adapts to hypoxic and ER stress environments is crucial for developing targeted therapies, as these tumors rely on specific metabolic pathways for survival.
• What they did: The study analyzed NEPC samples and found PIKfyve is overexpressed; it functions in lysosomal degradation and lipid recycling, supporting tumor adaptation under hypoxia.
• The result: Dual inhibition of PIKfyve and FASN synergistically increases ER stress, triggers tumor cell death, and offers a promising strategy to target NEPC’s stress-adaptive metabolic vulnerabilities.