@entity984 mutations are the most common mutations in non-small cell lung cancer (NSCLC) with adenocarcinoma histology. @entity984 mutations result in the activation of the RAF- @entity8047 -ERK pathway, and agents that target RAF- @entity8047 -ERK pathways have been investigated in @entity984 mutant NSCLC. The two agents furthest in development are @entity17528 and @entity5459 . @entity5459 has greater binding for the @entity16629 allosteric site, and generally has superior pharmacokinetics. A randomized phase II trial of @entity1205 with and without @entity17528 revealed that the combination resulted numerically superior overall survival, and a statistically significant improvement in progression-free survival and objective response rate. However, a concerning rate of hospital admission, grade 3 or 4 neutropenia, and febrile neutropenia was observed with the combination. Trials have investigated @entity8047 inhibitors as single agents and in combination with @entity3866 , and the data do not support the further development. The activity of @entity8047 inhibitors appears to be similar in @entity1 with @entity984 mutant and wild-type NSCLC suggesting @entity984 mutation status is not a reliable biomarker for efficacy. It is possible that mutations of genes in addition to @entity984 mutations impact the activity of @entity8047 inhibitors, or specific subsets of @entity984 mutations may be resistant or susceptible to @entity8047 inhibition. Other potential explanations are gene amplifications, alternative RNA splicing of genes resulting in activation of their protein products, and deregulation of noncoding RNAs and consequent altered protein expression.

XXXX inhibition in non-small cell lung cancer.

@entity1 :: ('9606', 'Species') :: ['patients'] @entity8047 :: ('5609', 'Gene') :: ['MEK'] @entity5459 :: ('MESH:C560077', 'Chemical') :: ['Trametinib', 'trametinib'] @entity984 :: ('3845', 'Gene') :: ['KRAS'] @entity16629 :: ('5604;5605', 'Gene') :: ['MEK1/2'] @entity17528 :: ('MESH:C517975', 'Chemical') :: ['selumetinib'] @entity1205 :: ('MESH:C067311', 'Chemical') :: ['docetaxel'] @entity3866 :: ('MESH:C400278', 'Chemical') :: ['erlotinib']
@entity8047 :: (5609,Gene) :: ['MEK']
