The EGFR-mediated signaling pathways through PTPN11 (SHP2) and AKT1S1 (PRAS40), along with the enhanced anti-apoptotic signaling pathways resulting from acquired resistance to cetuximab, provide multiple opportunities for identifying and validating biomarkers, signaling pathways, and resistance mechanisms for clinical improvements in cancer treatment [53]. The gene discussed is AKT1S1; the disease is cancer.