Context defines precision: rethinking KRAS inhibition in oncology.

The recent breakthroughs in KRAS inhibition have converted a previously "undruggable" oncogene into a viable therapeutic target. However, the inconsistency in clinical responses across tumor types highlights that mutation alone is not sufficient to predict therapeutic outcomes. This Perspective introduces a multidimensional framework that uniquely integrates KRAS mutational status with tissue, co-mutation, signaling, and immune context to inform rational trial design, predictive biomarker development, and the advancement of KRAS-targeted therapies.