EGFR and cancer: Cancer cell cultures established in vitro from gefitinib/erlotinib-afatinib-osimertinib-resistant tumor xenografts were used to study the functional significance of increased expression of the Hh pathway components by investigating the effect of SMO inhibition, with the use of a selective SMO antagonist, sonidegib, on cell proliferation and apoptosis, in the presence or absence of EGFR-TKIs (Figure 5B).