The combined blockade of Hh and EGFR by the SMO antagonist, sonidegib, and the respective EGFR-TKI significantly decreased the metastatic behavior of resistant cancer cells established in vitro from resistant xenografts, thus revealing that Hh is implicated in the induction of EMT in models of acquired resistance to EGFR inhibitors of first-, second- and third-generation. Here, EGFR is linked to cancer.