A friendly approach to personalized treatment in lung adenocarcinoma

Abstract

Lung cancer is a lethal disease with most cases already disseminated at time of diagnosis. Driver mutations in the epidermal growth factor receptor (EGFR) tyrosine kinase (TK) domain have been identified in lung adenocarcinomas, mostly in never smokers with frequencies ranging from 20-60% in this group. Treatment with EGFR TK inhibitors (TKIs) (gefitinib or erlotinib) achieves 70% res- ponses with progression-free survival (PFS) of 9-13 months, though there are subgroups of patients with long lasting remissions. Further evaluable is the presence of a second mutation: T790M, identified as an acquired resistance mutation, can be initially present, possibly indicating a genetically distinct disease. Also, genetic modifiers including BRCA1 and components of the NFКB pathway predict response to EGFR TKIs. A novel field of research is several genes which act as downregulators of BRCA1 expres- sion, therefore permitting the predictive model based on BRCA1 mRNA expression to be further refined. Although there is not yet any experience, re-biopsies at time of clinical progression are warranted in the majority of patients with EGFR mutations since several genetic changes can be identified which can lead to innovative therapeutic approaches