BTK and non-small cell lung carcinoma: Two main reasons may explain the potency of RN486: i) RN486 is a reversible allosteric BTK inhibitor that interact with K430 [42], a residue critical for protein kinase activity [43], and does not cross react with EGFR family member, being therefore specific for BTK only; ii) Ibrutinib is metabolized and inactivated by the two isoforms of the CYP3 detoxifying enzyme 3A4 and 3A5 [44], both of them overexpressed in NSCLC [45].