Overcoming therapy resistance in EGFR-mutant lung cancer

Passaro, Antonio; Jänne, Pasi A.; Mok, Tony; Peters, Solange

doi:10.1038/s43018-021-00195-8

Cited by 565Lung Cancer Treatments and MutationsHER2/EGFR in Cancer ResearchCancer Genomics and Diagnostics

Overcoming therapy resistance in EGFR-mutant lung cancer

Passaro, Antonio, Jänne, Pasi A., Mok, Tony, Peters, Solange·2021·Nature Cancer

DOI 10.1038/s43018-021-00195-8

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Abstract

Tyrosine kinase inhibitors (TKIs) have dramatically changed the clinical prospects of patients with non-small cell lung cancer harboring epidermal growth factor receptor (EGFR)-activating mutations. Despite prolonged disease control and high tumor response rates, all patients eventually progress on EGFR TKI treatment. Here, we review the mechanisms of acquired EGFR TKI resistance, the methods for monitoring its appearance, as well as current and future efforts to define treatment strategies to overcome resistance.

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C797X mutations account for 15% of resistance to second-line osimertinib because osimertinib requires Cys797.
“However, osimertinib depends on Cys797 for covalent binding, and C797X mutations account for 15% of cases of resistance to second-line osimertinib50–52.”
From Advances in covalent drug discovery (2022) · cites this paper as [50]

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Authors: Passaro, A., Jänne, P. A., Mok, T., & Peters, S.
Affiliations: European Institute of Oncology (IT)
Chinese University of Hong Kong (HK)
Centre Hospitalier Universitaire Vaudois (CH)
Corresponding author: Passaro, Antonio
ORCID: Passaro, Antonio
Mok, Tony
Peters, Solange
Venue: Nature Cancer
Publisher: Springer Science and Business Media LLC
Published: 2021-04-15
Volume: 2
Issue: 4
Pages: 377-391
ISSN: 2662-1347 (ISSN-L)
DOI: 10.1038/s43018-021-00195-8
OpenAlex: W3154466284
Semantic Scholar: e735c1242b465eb091c3603e81360d3c7109b1a7
Cited by: 565
References: 38
Citations by year: 2026: 96 · 2025: 147 · 2024: 120 · 2023: 123 · 2022: 64 · 2021: 15
FWCI: 13.12
Type: journal article
Language: en
Open access: closed
Licence: www.springernature.com/gp/researchers/text-and-data-mining (tdm)
www.springernature.com/gp/researchers/text-and-data-mining (vor)
Locations: Nature Cancer (publishedVersion)
PubMed (publishedVersion)
IRIS (submittedVersion)
SERVAL (Université de Lausanne) (submittedVersion)
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-mutant lung cancer, non-small cell lung cancer, EGFR tyrosine kinase inhibitors, acquired drug resistance, resistance mechanisms, disease surveillance, anti-EGFR therapy, clinical trials
MeSH terms: Carcinoma, Non-Small-Cell Lung, Humans, Lung Neoplasms, Mutation, Drug Resistance, Neoplasm, Protein Kinase Inhibitors, ErbB Receptors

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Overcoming therapy resistance in EGFR-mutant lung cancer

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