MCL1 and non-small cell lung carcinoma: The mechanisms of intrinsic (primary) TKI resistance are not fully understood, but paxillin (PXN) overexpression confers intrinsic TKI resistance in NSCLC via modulation of Mcl-1 and BIM protein stability due to ERK activation.6 The combination of TKI with the ERK inhibitor selumetinib is reported to improve TKI sensitivity and outcomes in cell and animal models.7, 8 Unfortunately, no benefit has yet been established for combining an ERK inhibitor and a TKI as a treatment for NSCLC patients.