Findings from this proof-of-principle study showed that RAC1-amplified head and neck cancer patient-derived xenografts (but not RAC1-diploidy tumors), and engineered RAC1-A159V HNSCC xenografts (but not engineered RAC1-P29S HNSCC xenografts) were both sensitive to Rac targeting in vivo with a preclinical Rac inhibitor, EHop-16. Here, AKT1 is linked to head and neck cancer.