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Rare epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer.

Authors
  • Harrison, Peter T1
  • Vyse, Simon1
  • Huang, Paul H2
  • 1 Division of Molecular Pathology, The Institute of Cancer Research, London, SW3 6JB, UK.
  • 2 Division of Molecular Pathology, The Institute of Cancer Research, London, SW3 6JB, UK. Electronic address: [email protected]
Type
Published Article
Journal
Seminars in Cancer Biology
Publisher
Elsevier
Publication Date
Apr 01, 2020
Volume
61
Pages
167–179
Identifiers
DOI: 10.1016/j.semcancer.2019.09.015
PMID: 31562956
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Epidermal growth factor receptor (EGFR) mutations are the second most common oncogenic driver event in non-small cell lung cancer (NSCLC). Classical activating mutations (exon 19 deletions and the L858R point mutation) comprise the vast majority of EGFR mutations and are well defined as strong predictors for good clinical response to EGFR tyrosine kinase inhibitors (EGFRi). However, low frequency mutations including point mutations, deletions, insertions and duplications occur within exons 18-25 of the EGFR gene in NSCLC and are associated with poorer responses to EGFRi. Despite an increased uptake of more sensitive detection methods to identify rare EGFR mutations in patients, our understanding of the biology of these rare EGFR mutations is poor compared to classical mutations. In particular, clinical data focused on these mutations is lacking due to their rarity and challenges in trial recruitment, resulting in an absence of effective treatment strategies for many low frequency EGFR mutations. In this review, we describe the structural and mechanistic features of rare EGFR mutations in NSCLC and discuss the preclinical and clinical evidence for EGFRi response for individual rare EGFR mutations. We also discuss EGFRi sensitivity for complex EGFR mutations, and conclude by offering a perspective on the outstanding questions and future steps required to make advances in the treatment of NSCLC patients that harbour rare EGFR mutations. Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.

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