For example, mutations in the MAPK pathway components KRAS [82,99,131,144,145], NRAS [79,98], BRAF [79,98,132,140] and MEK [132,146], as well as reduced DUSP6 (a MAPK phosphatase) [144] and mutations in the RAS negative regulators neurofibromin 1 and 2 (NF1/2) [99,127], cause ALK TKI resistance in NSCLC. The gene discussed is ALK; the disease is non-small cell lung carcinoma.