Rare epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer.
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Date
2020-04-01Author
Harrison, PT
Vyse, S
Huang, PH
Type
Journal Article
Metadata
Show full item recordAbstract
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.
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Subject
Humans
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Genetic Predisposition to Disease
Amino Acid Substitution
Mutation
Alleles
Exons
Genetic Association Studies
ErbB Receptors
Research team
Molecular and Systems Oncology
Language
eng
Date accepted
2019-09-20
License start date
2020-04
Citation
Seminars in cancer biology, 2020, 61 pp. 167 - 179
Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD