EGFR and hepatocellular carcinoma: This paradox suggests that pathway activation in HCC is largely driven by alternative mechanisms, including overexpression or constitutive activation of upstream receptor tyrosine kinases (such as EGFR, FGFR, and c-Met), amplification of autocrine or paracrine growth factor signaling, and suppression of negative regulators like Sprouty and dual-specificity phosphatases (DUSPs).