The impact of rare EGFR mutations on the treatment response of patients with non-small cell lung cancer

Abstract

Mutational activation of the epidermal growth factor receptor (EGFR) gene is implicated in lung cancer; clinical and cancer genome sequencing studies have identified hundreds of mutations in the protein kinase domain. EGFR mutation testing usually focuses on common mutations like the exon 19 deletion and exon 21 point mutation (L858R). However, molecular screening methods have started to extend beyond identification of classic EGFR mutations to prevent exclusion of patients with rare or complex mutations who may benefit from anti-EGFR therapy. Rare EGFR-mutated non-small-cell lung cancers are heterogeneous: exon 20 insertions lack sensitivity to tyrosine kinase inhibitors while exon 18 or complex mutations are more sensitive and require individual assessment. Until testing for uncommon EGFR mutations evolves and studies with large number of patients are performed, knowledge of this field will remain limited.

Keywords:

• epidermal growth factor receptor mutations
• exon 18 mutations
• exon 20 mutations
• non-small-cell lung cancer
• tyrosine-kinase inhibitors

Financial & competing interests disclosure

Work in R Rosell’s laboratory was partially supported by grants from the La Caixa Foundation and Red Tematica de Investigacion Cooperativa en Cancer (RTICC; grant RD12/0036/0072). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.