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Uncommon Epidermal Growth Factor Receptor mutations in non-small cell lung cancer and their mechanisms of EGFR tyrosine kinase inhibitors sensitivity and resistance
Abstract
Therapy targeted against the epidermal growth factor receptor (EGFR) has demonstrated dramatic tumor responses and favorable clinical outcomes in a select group of non-small cell lung cancer (NSCLC) patients whose tumors harbor EGFR activating mutations. The best characterized of the mutations conferring sensitivity to EGFR tyrosine kinase inhibitors (TKIs) are deletions in exon 19 and a point mutation in exon 21 (L858R). Likewise, the most common mutation that confers resistance is the T790M point mutation. However several other mutations have been reported and several have been characterized as regards their role in sensitivity or resistance to EGFR TKIs. Resistance to the EGFR TKIs erlotinib and gefitinib, and the newer irreversible EGFR TKIs is a problem of fundamental importance. Recognition of the presence and significance of specific EGFR mutations is important for appropriate therapeutic implementation of EGFR TKIs and research and development of mutation-specific inhibitors. We summarize the literature and present an overview of the subject of less common EGFR mutations and their clinical significance, with an emphasis on EGFR TKI sensitivity or resistance.
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Metadata
- Authors
- Massarelli, E., Johnson, F. M., Erickson, H. S., Wistuba, I. I., & Papadimitrakopoulou, V.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- Corresponding author
- Papadimitrakopoulou, Vassiliki
- Venue
- Lung Cancer
- Publisher
- Elsevier BV
- Published
- 2013-06
- Volume
- 80
- Issue
- 3
- Pages
- 235-241
- ISSN
- 0169-5002 (ISSN-L)
- OpenAlex
- W2014993624
- Cited by
- 110
- References
- 86
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 9 · 2023: 5 · 2022: 16 · 2021: 8 · 2020: 11 · 2019: 9 · 2018: 8 · 2017: 7 · 2016: 8 · 2015: 8 · 2014: 10 · 2013: 4
- FWCI
- 1.56
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Lung Cancer (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Keywords
- EGFR mutation, non-small cell lung cancer, EGFR tyrosine kinase inhibitors, drug resistance, erlotinib, gefitinib, exon 19 deletion, L858R mutation, T790M mutation, targeted therapy
- MeSH terms
- Antineoplastic Agents, Carcinoma, Non-Small-Cell Lung, Exons, Humans, Point Mutation, Drug Resistance, Neoplasm, Protein Kinase Inhibitors, ErbB Receptors
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