RAC1-Amplified and RAC1-A159V Hotspot-Mutated Head and Neck Cancer Sensitive to the Rac Inhibitor EHop-016 In Vivo: A Proof-of-Concept Study.

ABSTRACT: Objective:RAC1 aberrations in head and neck squamous cell carcinoma (HNSCC) remain clinically inactionable today. Methods: Here, we investigated the clinical significance and potential druggability of RAC1 genomic aberrations in HNSCC. Results: Notably, HPV(-)HNSCC patients bearing the unique HNSCC-prevalent RAC1-A159V hotspot mutation, P29S hotspot and G-box domain mutations, and RAC1 copy number increases all displayed dismal overall survival (TCGA-HNSCC). Here, we demonstrated that all five HNSCC patient-relevant RAC1 aberrations tested (A159V and P29S hotspot mutations, K116N, G15S, and N39S) could significantly drive HNSCC tumoroid growth and/invasion, with A159V, P29S, and K116N mutants being the most potent drivers. Interesting

SUBMITTER: Chan HHY 

PROVIDER: S-EPMC11816149 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature