The DOI matches its Crossref record; 19 of the 19 references it cites were found in a registry or an index.
Resistance mechanisms to osimertinib in EGFR-mutated non-small cell lung cancer
Open accessAbstract
Osimertinib is an irreversible, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that is highly selective for EGFR-activating mutations as well as the EGFR T790M mutation in patients with advanced non-small cell lung cancer (NSCLC) with EGFR oncogene addiction. Despite the documented efficacy of osimertinib in first- and second-line settings, patients inevitably develop resistance, with no further clear-cut therapeutic options to date other than chemotherapy and locally ablative therapy for selected individuals. On account of the high degree of tumour heterogeneity and adaptive cellular signalling pathways in NSCLC, the acquired osimertinib resistance is highly heterogeneous, encompassing EGFR-dependent as well as EGFR-independent mechanisms. Furthermore, data from repeat plasma genotyping analyses have highlighted differences in the frequency and preponderance of resistance mechanisms when osimertinib is administered in a front-line versus second-line setting, underlying the discrepancies in selection pressure and clonal evolution. This review summarises the molecular mechanisms of resistance to osimertinib in patients with advanced EGFR-mutated NSCLC, including MET/HER2 amplification, activation of the RAS–mitogen-activated protein kinase (MAPK) or RAS–phosphatidylinositol 3-kinase (PI3K) pathways, novel fusion events and histological/phenotypic transformation, as well as discussing the current evidence regarding potential new approaches to counteract osimertinib resistance.
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Cites
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Third-generation EGFR and ALK inhibitors: mechanisms of resistance and management
Cooper, A. J., Sequist, L. V., & Lin, J. J. (2022) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-022-00639-9 · Cited by 508
Amivantamab plus Lazertinib in Previously Untreated EGFR -Mutated Advanced NSCLC
Cho, B. C., Lu, S., Felip, E., Spira, A. I., Girard, N., Lee, J.-S., Lee, S.-H., Ostapenko, Y., Danchaivijitr, P., Liu, B., et al. (2024) · New England Journal of Medicine · doi:10.1056/nejmoa2403614 · Cited by 458
Metadata
- Authors
- Leonetti, A., Sharma, S., Minari, R., Perego, P., Giovannetti, E., & Tiseo, M.
- Venue
- British Journal of Cancer
- Published
- 2019-09-30
- Volume
- 121
- Issue
- 9
- Pages
- 725-737
- ISSN
- 0007-0920 (ISSN-L)
- 1532-1827
- OpenAlex
- W2976334328
- Cited by
- 1,409
- References
- 19
- FWCI
- 79.40
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Leonetti, A., Sharma, S., Minari, R., Perego, P., Giovannetti, E., & Tiseo, M. (2019). Resistance mechanisms to osimertinib in EGFR-mutated non-small cell lung cancer. British Journal of Cancer. https://doi.org/10.1038/s41416-019-0573-8
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