Cannabinoid-driven epigenetic remodeling of a chromatin-lipid homeostatic axis via ARID1A uncovers a metabolic vulnerability in cancer

These alterations have spurred extensive efforts to uncover vulnerabilities associated with ARID1A deficiency. However, emerging studies suggest that ARID1A may also exert context-dependent tumor-promoting functions, opening new therapeutic avenues in ARID1A-proficient tumors.

In endometrial cancer (EC), ARID1A mutations typically arise late during tumor progression and are dispensable for tumor initiation, providing a relevant context to interrogate its noncanonical homeostatic roles. Here, through integrated multiomics analyses, cellular bioenergetics and in vivo studies using EC patient-derived xenografts and genetically engineered mouse models, we demonstrate that functional ARID1A is required for acquired resistance to nutrient deprivation induced by antiangiogenic (starvation) therapy.