MAPK1 E322K

The crystal structure of ERK2 E322K also indicated a disturbed dimer interface, and reduced dimerization was detected by a two-hybrid test; yet, it was detected in dimers in EGF-treated cells, although to a lesser extent than D321N or wt ERK2. These findings indicate a range of small differences in behaviors that may contribute to increased function of E322K in certain cancers.

"In vitro studies found this mutation to be associated with resistance to dabrafenib, trametinib, but potential sensitivity to ERK inhibitors...One patient with NSCLC harboring a concurrent EGFR L858R mutation did not respond to erlotinib...Two patients had TMB score of 100.9 and 12.9 mutation/Mb had partial response to pembrolizumab... ERK2 E322K mutation is a rare oncogenic mutation across diverse solid tumor types, associated with a high co-occurrence of other activating mutations and a high TMB. The lack of response to other targeted therapies suggests ERK2 E322K is a potential driver mutation. These findings may inform treatment and further development of ERK inhibitors."