AKT1 and head and neck squamous cell carcinoma: Moreover, loss-of-function PBRM1 mutations attenuate the effects of EGFR inhibition in part by sustaining Akt signaling [89], implying a role of PBRM1 not only as a biomarker of immune checkpoint inhibitor response, but also as a potential modifier of EGFR dependency.While these genes represent potential action points to modulate an ErbB-driven co-regulon in head and neck squamous cell carcinoma, the simultaneous overexpression of multiple ErbB receptors in most cases [15] suggests that concurrent modulation of multiple ErbB family members could be biologically and clinically meaningful.