Proto-oncogene tyrosine-protein kinase ROS (ROS1) G2032R mutant (ROS1 G2032R)

The ROS1 G2032R mutant is a clinically significant variant of the Proto-oncogene tyrosine-protein kinase ROS, a receptor tyrosine kinase involved in regulating cell growth, differentiation, and survival (1.4.3). In certain cancers, particularly non-small cell lung cancer (NSCLC), ROS1 gene rearrangements create oncogenic fusion proteins that drive malignant progression (1.3.1). The G2032R mutation typically arises as an acquired resistance mechanism following treatment with first-line tyrosine kinase inhibitors (TKIs) like crizotinib (1.2.3). Located at the solvent front of the kinase domain, the substitution of glycine with a bulky arginine residue creates steric hindrance that prevents many standard TKIs from binding effectively to the ATP-binding pocket (1.3.1, 1.3.4). This mutation represents a major therapeutic challenge, necessitating the use of next-generation TKIs such as repotrectinib and NVL-520, which are specifically designed to bypass this structural interference (1.1.1, 1.2.1). Monitoring for this mutation via liquid or tissue biopsy is essential for guiding subsequent lines of therapy in ROS1-rearranged cancers (1.1.2, 1.3.2).

Other names

ROS1 p.G2032RROS1 Gly2032Argc-ros-1 G2032RROS proto-oncogene 1 G2032R

Tyrosine kinase inhibition