 Recently, resistance mechanisms that cause progression on TKI treatment been elucidated. The most common is the T790M mutation in EGFR, but other mechanisms such as increased MET and HER3 expression is also described. It is estimated that T790M mutations in EGFR accounts for 50 of the cases with TKI resistance development. With the exception of HER3 and MET, which is estimated to represent less than 5 of the cases with the development of resistance, are the mutations which cause the remaining 50 of cases, resistance remains unknown. The revelation of further resistance mutations hampered by the problems of obtaining biopsies when progression occurs. 