Heterogeneous Driving Effects Guide Personalized Tumor Treatments Targeting N6-methyladenosine.

Alterations to N6-methyladenosine modifications can promote malignant progression by modulating gene expression through regulation of transcript metabolism. Quantifying the causal impact of m6A dysregulation at the population level could help to guide personalized therapeutic interventions. Here, we developed a causal framework that enables precise estimation of the driving effects (DE) of m6A dysregulation on tumor survival, establishing DE-based enhanced prioritization rules for anti-m6A therapies.

Plasma membrane-associated ARAF condensates fuel RAS-related cancer drug resistance.

RAF protein kinases are major RAS effectors that function by phosphorylating MEK. Although all three RAF isoforms share a conserved RAS binding domain and bind to GTP-loaded RAS, only ARAF uniquely enhances RAS activity. Here we uncovered the molecular basis of ARAF in regulating RAS activation.