Cited by 109Lung Cancer Treatments and MutationsHER2/EGFR in Cancer ResearchLung Cancer Diagnosis and Treatment

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Targeting EGFR in Lung Cancer: Current Standards and Developments

Díaz-Serrano, Asunción, Gella, Pablo, Jiménez, Elisabeth, Zugazagoitia, Jon, Paz-Ares Rodríguez, Luis·2018·Drugs

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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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Cancer Statistics, 2017.
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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.”
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Huang, M.-H., Lee, J., Hung, P.-S., & Yang, J. C. (2022) · JTO Clinical and Research Reports · doi:10.1016/j.jtocrr.2022.100405 · Cited by 10
“EGFR tyrosine kinase inhibitors (TKIs) such as gefitinib, erlotinib, and afatinib are the standard therapies for patients with advanced NSCLC with tumor cells carrying specific EGFR mutations.(9) All patients eventually develop acquired resistance to first- or second-generation EGFR TKIs, and new-generation EGFR T790M…”
Background
Small-Molecule Anti-Cancer Drugs From 2016 to 2020: Synthesis and Clinical Application
Wang, L., Li, R., Song, C., Chen, Y., Long, H., & Yang, L. (2021) · Natural Product Communications · doi:10.1177/1934578x211040326 · Cited by 11
“Unlike firstgeneration EGFR TKIs (gefitinib and erlotinib), dacomitinib, as a second-generation EGFR TKIs, was designed to overcome some of the issues related to the acquired resistance caused by first-generation agents.(50,51) The dacomitinib (XVII) synthesis process was reported by Pfizer, as shown in Scheme 18.”
Background
In silico and in vitro investigation of dual targeting Prima-1 MET as precision therapeutic against lungs cancer
Meher, R. K., Mir, S. A., & Anisetti, S. S. (2023) · Journal of Biomolecular Structure and Dynamics · doi:10.1080/07391102.2023.2219323 · Cited by 10
“Adenocarcinoma, SCC and large cell carcinoma are some of the obsolete and overly simplistic histological classifications for NSCLC.”
BackgroundInfluential
Strategies for enhancing non-small cell lung cancer treatment: Integrating Chinese herbal medicines with epidermal growth factor receptor-tyrosine kinase inhibitors therapy
Chen, L., Chen, W.-D., Xu, Y.-X., Ren, Y., Zheng, C., Lin, Y.-Y., & Zhou, J. (2024) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2024.176871 · Cited by 9
Imaging-Based Surrogate Markers of Epidermal Growth Factor Receptor Mutation in Lung Adenocarcinoma: A Local Perspective
Algharras, A., Kovacina, B., Tian, Z., Alexander, J. W., Semionov, A., van Kempen, L. C. L. T., & Sayegh, K. (2020) · Canadian Association of Radiologists Journal · doi:10.1177/0846537119888387 · Cited by 9
Idylla EGFR assay on extracted DNA: advantages, limits and place in molecular screening according to the latest guidelines for non-small-cell lung cancer (NSCLC) patients
Khalifa, E., Chapusot, C., Tournier, B., Sentis, J., Marion, E., Remond, A., Aubry, M., Pioche, C., Bergeron, A., Primois, C., et al. (2022) · Journal of Clinical Pathology · doi:10.1136/jcp-2022-208325 · Cited by 9
Recent advances in molecular targeted therapy of lung cancer: Possible application in translation medicine.
Salmani-Javan, E., Jadid, M. F. S., & Zarghami, N. (2024) · PubMed Central · doi:10.22038/ijbms.2023.72407.15749 · Cited by 8
“Second-generation agents such as Afatinib, covalently bind to the kinase domain of EGFR (116).”
Background
An afatinib-based theranostic fluorescent probe for cancer cells and its applications in monitoring pH changes during treatment
Wang, K., Wen, H., Liu, C., Li, Z., Wang, S., Zhu, H., Liu, M., Rong, X., Yu, M., Sheng, W., et al. (2024) · Sensors and Actuators B Chemical · doi:10.1016/j.snb.2024.137056 · Cited by 7
Concurrent inhibition of ErbB family and MEK/ERK kinases to suppress non-small cell lung cancer proliferation.
Lin, X., Liao, J., Geng, X., Dan, H., & Chen, L. (2020) · PubMed Central · Cited by 7
Clinical factors affecting the long-term survival of breast cancer patients
Li, Y., Wang, X., Shen, J., Ma, L., Wang, C., He, K., Liu, D., & Li, Y. (2023) · Journal of International Medical Research · doi:10.1177/03000605231164004 · Cited by 6
Advances in the treatment of brain metastases in EGFR-mutant non-small cell lung cancer
Wang, H., Wang, L., Gao, N., Li, H., Yang, F., Liu, Z., Li, H., & Li, X. (2025) · Lung Cancer · doi:10.1016/j.lungcan.2025.108641 · Cited by 6
Metabolism and pharmacokinetic study of deuterated osimertinib
Zhan, X., Bao, S., Li, X., Zhou, S., Dahar, M. R., Lin, N., Chen, X., Niu, C., Ji, K., Wu, Y., et al. (2023) · Biopharmaceutics & Drug Disposition · doi:10.1002/bdd.2347 · Cited by 5
“Metabolic enzymes such as CYP1A, CYP2A, and CYP2C are also involved in its metabolism (Dickinson et al., 2016).”
Background
Precise Genotyping Via Surface‐Enhanced Raman Spectroscopy‐Based Optical Sensing Chip for Guiding Targeted Therapy in Lung Cancer
Fan, M., Chen, J., Zheng, X., Xu, L., Ye, J., Lin, X., Kong, K. V., Lin, D., Lu, Y., & Feng, S. (2024) · Laser & Photonics Review · doi:10.1002/lpor.202401400 · Cited by 5
Multimodal prediction of tyrosine kinase inhibitors therapy outcomes in advanced EGFR-mutated NSCLC patients
Chai, X., Li, H., Yang, M., Zeng, J., Chen, G., Li, Y., Wang, W., Liu, Z., Li, K., Zhang, T., et al. (2025) · Journal of Translational Medicine · doi:10.1186/s12967-025-06956-8 · Cited by 5
Novel pyridine-heterocycle hybrids: synthesis via Hantzsch and Biginelli reactions, docking simulations, and anticancer activity
Diab, H. M., Salem, M. E., Elwahy, A. H. M., Ragheb, M. A., Noamaan, M. A., Algethami, F. K., Abdelhamid, I. A., & Mahmoud, H. K. (2026) · RSC Advances · doi:10.1039/d6ra00243a · Cited by 4
Supplementation with Fish Oil and Selenium Protects Lipolytic and Thermogenic Depletion of Adipose in Cachectic Mice Treated with an EGFR Inhibitor
Wang, H., Chan, Y.-L., Chiu, Y., Wu, T., Hsia, S., & Wu, C. (2024) · Cells · doi:10.3390/cells13171485 · Cited by 5
MicroRNAs and lung cancer: overview of essential pathways and somatic mutations in cancer progression
Tirpe, A., Nutu, A. M., Busuioc, C. I., Pop, O. L., & Berindan‐Neagoe, I. (2025) · Frontiers in Oncology · doi:10.3389/fonc.2025.1677471 · Cited by 5
“Activating EGFR mutations are druggable via EGFR TKIs, classi ﬁ ed in ﬁ rst-generation EGFR TKIs, such as ge ﬁ tinib and erlotinib and second-generation TKI afatinib (20).”
Sophora compounds against non-small cell lung cancer: Research status and mechanisms
Ye, B., Lin, C., Huang, H., Chen, P., Liu, X., Wang, K., Zhang, H., Liu, J., Zhang, C., & Li, L. (2025) · Phytomedicine · doi:10.1016/j.phymed.2025.156890 · Cited by 3
Challenges in the management of advanced NSCLC among Italian oncologists: a 2019 national survey unfolds regional disparities
Giglio, A. D., Orlando, V., Andrini, E., Ricciuti, B., Lamberti, G., & Chiari, R. (2022) · Tumori Journal · doi:10.1177/03008916211069412 · Cited by 3
Les avancées dans la prise en charge des cancers bronchopulmonaires : ce qui change pour le réanimateur
Pinsolle, J., Terzi, N., Ferrer, L., Levra, M. G., Toffart, A., & Moro‐Sibilot, D. (2019) · Médecine Intensive Réanimation · doi:10.3166/rea-2019-0091 · Cited by 4
Non-small cell lung cancer after EGFR-TKI resistance: from drug resistance mechanisms to precision interventions
Wang, Z., Song, Y., Wang, A., & 刘宝山 (2026) · Frontiers in Pharmacology · doi:10.3389/fphar.2026.1795614 · Cited by 2
Natural products combating EGFR-TKIs resistance in cancer
Li, X., Zhu, G., Peng, Q., Li, X., Zou, X., Zhang, W., Zhao, L., Li, X., Wu, P., Luo, A., et al. (2025) · European Journal of Medicinal Chemistry Reports · doi:10.1016/j.ejmcr.2025.100251 · Cited by 2
Alectinib causes sinus bradycardia by suppressing L-type calcium current in sinus node
Liu, G.-X., Diao, F., Lu, G., Zheng, Q., Fu, B., Jiao, H., Wang, K.-Z., & Liu, D.-H. (2025) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2025.177527 · Cited by 2
Recent Approaches on Oncolytic Viruses, Aptamers, TTFields and Personalized Treatment used for the Management of Glioblastoma: A Comprehensive Review
Singh, A., Kanda, A., & Kanda, J. (2025) · Anti-Cancer Agents in Medicinal Chemistry · doi:10.2174/0118715206364677250401190214 · Cited by 3
Inhibitors as a therapeutic frontier in lung cancer: Mechanism, opportunities, and molecular docking studies
Patel, R., Rathod, D., Shah, N. J., Vaghela, V., & Patadiya, N. (2025) · Computers in Biology and Medicine · doi:10.1016/j.compbiomed.2025.110889 · Cited by 3
Response of Leptomeningeal Metastases in EGFR-Mutated Non-Small-Cell Lung Cancer to Afatinib in the Absence of Radiotherapy
Quintero, N. E. L., González-Hoyos, D., Yepes, A., Herrera, D. A., Peláez, S., Caicedo-Zamudio, C., Blanco-Daza, E., & López, J. C. (2019) · Case Reports in Oncological Medicine · doi:10.1155/2019/1939703 · Cited by 2
“EGFRmutations are observed in 15% of lung cancer cases and have been associated with metastatic tropism to the brain, as well as to predict sensitivity to tyrosine kinase inhibitors (TKIs) [3, 5, 7, 8, 13, 25].”
Background
The Frequency of Epidermal Growth Factor Receptor (EGFR) Mutation in Patients with Lung Adenocarcinoma Referred to a Lung Diseases Hospital; A Cross-Sectional Study from Iran
Mohammadi, S., Rezaei, M., Shojaeian, F., Pourabdollah, M., Ziazi, L. M., Seifi, S., Doroodinia, A., Salimi, B., Khosravi, A., & Farhangnasab, M. A. (2022) · Iranian journal of pathology · doi:10.30699/ijp.2022.533427.2673 · Cited by 2
Oncogenes
Pierotti, M. A., Frattini, M., Epistolio, S., Sozzi, G., & Croce, C. M. (2022) · Holland‐Frei Cancer Medicine · doi:10.1002/9781119000822.hfcm004.pub2 · Cited by 2
Discovery of Novel EGFR Kinase Inhibitors Using a Wild-Type EGFR: A Computational ApproachPreprint
Maji, D. (2025) · ChemRxiv · doi:10.26434/chemrxiv-2025-k329j · Cited by 2
Recent Insights into Osimertinib Analogues against EGFR Positive Non-small Cell Lung Cancer
Chhabra, J., Kashyap, P., Pahwa, R., Narang, R., Dureja, H., Lal, S., & Verma, S. (2023) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026623666230602143605 · Cited by 1
CAR-T cell therapy for the treatment of lung cancer: Current challenges and emerging therapeutic strategies
Shi, D., Yan, X., Liu, J., Chen, H., Wang, X., Li, R., Tian, X., Lin, X., & Wang, Y. (2025) · Lung Cancer · doi:10.1016/j.lungcan.2025.108849 · Cited by 1
Tyrosine kinase inhibitors and cardiovascular toxicity: a focused review
Zheng, H. (2025) · Cardiology Plus · doi:10.1097/cp9.0000000000000136 · Cited by 1
QT Prolongation and Arrhythmias in Cancer Therapy: A Narrative Review of Mechanistic and Clinical Studies
Ogunniyi, K. E., Djunadi, T. A., Ayedun, S. A., Onyenokwe, V., Okuma, O. A., Sanji, E. W., & Greek, A. (2026) · Cardiovascular Toxicology · doi:10.1007/s12012-026-10130-x · Cited by 1
“…the risk of ventricu - lar arrhythmias, suggesting that additional patient-spe - cific and pharmacologic factors contribute to arrhythmic risk [ 36,38] Anaplastic Lymphoma Kinase (ALK) inhibitors ALK inhibitors are generally associated with a lower incidence of clinically significant QTc…”
Liposomal drug delivery for lung cancer therapy: progress, challenges, and future perspectives
Vatankhah, A., Moghaddam, S. H., Rahmanian, M., Khosropanah, S., Oroojalian, F., Kesharwani, P., & Sahebkar, A. (2026) · Molecular Cancer · doi:10.1186/s12943-026-02728-0 · Cited by 1
EGFR-Targeted Nanoparticle Delivery of Osimertinib for Triple-Negative and Metastatic Breast Cancer Therapy
Alfagih, I. M., Alfagih, M., Almurshedi, A. S., Aldosari, B. N., AlQuadeib, B. T., Hajjar, B., Almogheerah, S., & Alzahrani, R. (2026) · Pharmaceutics · doi:10.3390/pharmaceutics18091179 · Cited by 1
“Its use is often associated with severe systemic side effects, including diarrhea, skin rashes, mucositis, and renal complications, limiting its long-term and widespread application [6,7].”
PCR-basierte Verfahren für die Muta - tionsdetektion bei Tumorpatienten
Werner, T. V., & Laßmann, S. (2018) · BIOspektrum · doi:10.1007/s12268-018-0964-z
Biocartis Idylla proves Fast and Accurate in Detecting Oncogenic KRAS and EGFR Mutations in Paraffin Embedded Tumor Samples
Brohawn, D. G., Mu, X., Tong, Z., Rao, E. M., Wang, Y., & Li, X. (2018)
Validity of an NGS‑based multiple gene panel in identifying actionable mutations for patients with NSCLC in a Chinese hospital
Cao, W., Yan, C., Wang, H., Tang, T., Wang, H., & Liu, D. (2019) · Oncology Letters · doi:10.3892/ol.2019.10265
“In the past decade, genetic and genomic profiling in NSCLC has improved considerably, and with it, the understanding of underlying molecular mechanisms of disease pathogenesis and strategies for targeted therapies (3-5).”
Background
La réanimation des patients cancéreux à l’heure de l’immunothérapie et des thérapies ciblées
Toffart, A., Pinsolle, J., Levra, M. G., Terzi, N., & Moro‐Sibilot, D. (2019) · Revue des Maladies Respiratoires Actualités · doi:10.1016/s1877-1203(19)30111-9
Nano Technological Approaches for Anti-tumour Therapy: Opportunities and Challenges
Champaneria, K., & Prajapati, P. (2020) · Nanoscience & Nanotechnology-Asia · doi:10.2174/2210681210666200213121156

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)
ORCID: Díaz-Serrano, Asunción
Venue: Drugs
Publisher: Springer Science and Business Media LLC
Published: 2018-06
Volume: 78
Issue: 9
Pages: 893-911
ISSN: 0012-6667 (ISSN-L)
1179-1950
DOI: 10.1007/s40265-018-0916-4
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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Targeting EGFR in Lung Cancer: Current Standards and Developments

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