Next, we investigated the mechanism of DT internalization by EGFR-mutant tumor cells in vivo. In its membrane-bound state HBEGF is the DT receptor (Naglich et al., 1992); yet, after cleavage from the cell membrane, soluble HBEGF is a high-affinity EGFR ligand that is upregulated by EGFR-mutant lung tumors (Jones et al., 1999; Yotsumoto et al., 2017). The gene discussed is EGFR; the disease is neoplasm.