EGFR and lung cancer: Interestingly, components of the Cullin 5 (CUL5)-RING E3 ligase (CRL5) complex (such as CUL5, RNF7 and UBE2F) as well as ARIH2, an Ariadne family RING-in-Between-RING (RBR) E3 ligase working together with CRL5, were amongst the positively selected hits, suggesting their previously unrecognized role in mediating EGFR TKI resistance in lung cancer.