The DOI matches its Crossref record; 151 of the 153 references it cites were found in a registry or an index.
Targeting EGFR in Lung Cancer: Current Standards and Developments
Abstract
Lung cancer is the second most common malignant tumor and the leading cause of cancer death. Epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) is a distinct subtype of lung cancer comprising approximately 15-40% of non-squamous tumors. The development of first- and second-generation EGFR tyrosine kinase inhibitors (TKIs) has been a significant step forward in the treatment of patients with EGFR-mutant tumors, and over the last few years has been the therapy of choice in the initial management of patients with activating mutations in EGFR, with some differences in efficacy and toxicity profile. Up to 50% of patients treated with first- and second-generation TKIs develop an EGFR exon 20 T790M mutation at the time of progression. In this context, osimertinib has shown a great benefit in terms of progression-free survival (PFS) in the second-line setting, including central nervous system metastasis control. The FLAURA trial, which compared osimertinib to first-generation inhibitors as first-line therapy, showed a clear PFS advantage for osimertinib and a trend towards an increased overall survival (OS) assessed by investigator review. Although T790M mutation is the most common mechanism of resistance to first- and second-generation EGFR TKIs, other EGFR-dependent and -independent mechanisms have been described, such as HER2 and MET amplifications or BRAF and MEK mutations. Some mechanisms of resistance to osimertinib and other third-generation TKIs have also been described. Several fourth-generation TKIs, targeted drug combinations and immunotherapy strategies are under investigation to overcome resistance to EGFR TKIs in order to improve EGFR-mutant NSCLC patient outcomes.
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“The anti-EGFR antibodies cetuximab and panitumumab are approved for the treatment of RAS/RAF wild type CRC(34, 35), while EGFR tyrosine kinase inhibitors (TKI) are approved for the treatment of EGFR mutant lung cancer(36).”
From EGFR Blockade Reverts Resistance to KRASG12C Inhibition in Colorectal Cancer. (2020) · cites this paper as [36]
In the citing paper
“Cetuximab sensitizes the KRAS (G12C) CRC cells to AMG510, and the combination restores secondary resistance to anti-EGFR antibodies.”
From Targeting KRAS mutant cancers: from druggable therapy to drug resistance (2022) · cites this paper as [104]
Citations
Cites
PD-1 and PD-L1 Immune Checkpoint Blockade to Treat Breast Cancer
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Adverse Renal Effects of Immune Checkpoint Inhibitors: A Narrative Review
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Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer
Borghaei, H., Paz-Ares, L., Horn, L., Spigel, D. R., Steins, M., Ready, N. E., Chow, L. Q., Vokes, E. E., Felip, E., Holgado, E., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1507643 · Cited by 9,335
Gefitinib or Carboplatin–Paclitaxel in Pulmonary Adenocarcinoma
Mok, T. S., Wu, Y.-L., Thongprasert, S., Yang, C.-H., Chu, D.-T., Saijo, N., Sunpaweravong, P., Han, B., Margono, B., Ichinose, Y., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0810699 · Cited by 8,261 · cited 2×
“After molecular studies identified EGFR mutations as predictive biomarkers for EGFR TKIs therapy response [28, 29], several preclinical and clinical trials showed enhanced activity of EGFR TKIs in EGFR-mutant NSCLC.”
Cell Signaling by Receptor Tyrosine Kinases
Lemmon, M. A., & Schlessinger, J. (2010) · Cell · doi:10.1016/j.cell.2010.06.011 · Cited by 7,929
Herbst, R. S., Baas, P., Kim, D.-W., Felip, E., Pérez-Gracia, J. L., Han, J.-Y., Molina, J., Kim, J.-H., Arvis, C. D., Ahn, M.-J., et al. (2016) · The Lancet · doi:10.1016/s0140-6736(15)01281-7 · Cited by 6,449
Comprehensive molecular profiling of lung adenocarcinoma
The Cancer Genome Atlas Research Network (2014) · Nature · doi:10.1038/nature13385 · Cited by 5,732
Gefitinib or Chemotherapy for Non–Small-Cell Lung Cancer with Mutated EGFR
Maemondo, M., Inoue, A., Kobayashi, K., Sugawara, S., Oizumi, S., Isobe, H., Gemma, A., Harada, M., Yoshizawa, H., Kinoshita, I., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa0909530 · Cited by 5,525
Osimertinib in Untreated EGFR -Mutated Advanced Non–Small-Cell Lung Cancer
Soria, J.-C., Ohe, Y., Vansteenkiste, J., Reungwetwattana, T., Chewaskulyong, B., Lee, K. H., Dechaphunkul, A., Imamura, F., Nogami, N., Kurata, T., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1713137 · Cited by 5,508
Cited by
Sorted by citations
Non‐small cell lung cancer in China
Chen, P., Liu, Y., Wen, Y., & Zhou, C. (2022) · 癌症：英文版 · doi:10.1002/cac2.12359 · Cited by 694
Sunder, S. S., Sharma, U. C., & Pokharel, S. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01469-6 · Cited by 572
“The AURA3 Randomized Phase III Study (Osimertinib vs PlatinumPemetrexed) and the FLAURA trial (osimertinib vs first-generation EGFR-TKI) in EGFR-Mutated Advanced non-small cell lung cancers (NSCLC) reported the frequency of LVD at 5% and 10%, respectively.(43) Paradoxically, a larger population study with a 2-year fol…”
BackgroundInfluentialEGFR Blockade Reverts Resistance to KRASG12C Inhibition in Colorectal Cancer.
Amodio, V., Yaeger, R., Arcella, P., Cancelliere, C., Lamba, S., Lorenzato, A., Arena, S., Montone, M., Mussolin, B., Bian, Y., et al. (2020) · Cancer Discovery · doi:10.1158/2159-8290.cd-20-0187 · Cited by 504
“The anti-EGFR antibodies cetuximab and panitumumab are approved for the treatment of RAS/RAF wild type CRC(34, 35), while EGFR tyrosine kinase inhibitors (TKI) are approved for the treatment of EGFR mutant lung cancer(36).”
BackgroundReceptor Tyrosine Kinase-Targeted Cancer Therapy
Yamaoka, T., Kusumoto, S., Ando, K., Ohba, M., & Ohmori, T. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19113491 · Cited by 297
“Several EGFR TKIs are currently available for cancer treatment [85].”
BackgroundTherapeutic advances of targeting receptor tyrosine kinases in cancer
Tomuleasa, C., Tigu, A.-B., Munteanu, R. A., Moldovan, C. S., Kegyes, D., Onaciu, A., Gulei, D., Ghiaur, G., Einsele, H., & Croce, C. M. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01899-w · Cited by 307
Metadata
- Authors
- Díaz-Serrano, A., Gella, P., Jiménez, E., Zugazagoitia, J., & Paz-Ares Rodríguez, L.
- Affiliations
- Research Institute Hospital 12 de Octubre (ES)
- Yale Cancer Center (US)
- Venue
- Drugs
- Published
- 2018-06
- Volume
- 78
- Issue
- 9
- Pages
- 893-911
- ISSN
- 0012-6667 (ISSN-L)
- 1179-1950
- OpenAlex
- W2809285875
- Semantic Scholar
- 3bfe42a82922c9b186444aa869784e8c1be89711
- Cited by
- 108
- References
- 153
- Citations by year
- 2026: 9 · 2025: 12 · 2024: 19 · 2023: 9 · 2022: 17 · 2021: 12 · 2020: 10 · 2019: 15 · 2018: 4
- FWCI
- 1.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Drugs (publishedVersion)
- PubMed (publishedVersion)
- BURJC Digital (King Juan Carlos University) (submittedVersion)
- Hispana (submittedVersion)
- Funders
- Consejería de Educación, Juventud y Deporte, Comunidad de Madrid (ES) and European Social Fund (PEJD16/2016/BMD-2715)
- Instituto de Salud Carlos III (CM15/00196)
- Sistema Nacional de Salud
- Universidad Complutense de Madrid
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
- Keywords
- EGFR-mutant non-small cell lung cancer, EGFR tyrosine kinase inhibitors, osimertinib, T790M mutation, acquired drug resistance, MET amplification, HER2 amplification, immunotherapy, FLAURA trial, central nervous system metastasis
- MeSH terms
- Acrylamides, Aniline Compounds, Antineoplastic Agents, Carcinoma, Non-Small-Cell Lung, Humans, Indoles, Lung Neoplasms, Piperazines, Pyrimidines, Disease Progression, Disease-Free Survival, Drug Resistance, Neoplasm, Protein Kinase Inhibitors, Molecular Targeted Therapy, ErbB Receptors
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