Cited by 110Lung Cancer Treatments and MutationsHER2/EGFR in Cancer ResearchCancer Genomics and Diagnostics

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Next-generation epidermal growth factor receptor tyrosine kinase inhibitors in epidermal growth factor receptor -mutant non-small cell lung cancer

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Tan, Chee-Seng, Cho, Byoung-Chul, Soo, Ross A.·2016·Lung Cancer

DOI 10.1016/j.lungcan.2016.01.003

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Abstract

Since the discovery of sensitizing EGFR mutations as a predictive marker of sensitivity to EGFR tyrosine kinase inhibitors (TKIs), the field of targeted therapy in non-small cell lung cancer (NSCLC) has been revolutionized. Patients harbouring these sensitizing mutations treated with EGFR TKI have derived significant clinical outcome when compared with standard platinum based chemotherapy doublets. However disease progression invariably occurs at a median of about 9-13 months from initiation treatment, if acquired resistance commonly due to the development of EGFR T790M mutation. A novel class of "third generation" EGFR TKIs have been developed that is sensitising and T790M mutant-specific whilst sparing WT EGFR, representing a significant breakthrough in the treatment in NSCLC patients with acquired resistance harboring these genotypes. Early phase clinical data suggest the third generation EGFR TKIs such as osimertinib, rociletinib, and HM61713 are highly efficacious and well tolerated. Another promising class of EGFR TKI such as AZD3759 has been designed to penetrate blood brain barrier to treat brain metastases and leptomeningeal disease and has showed promising responses in patients with brain metastases. Acquired resistance to third generation EGFR TKIs has been reported including EGFR C797S. Given its non-invasive nature, plasma ctDNA is being explored as a possible approach to detect T790M mutation and to also inform on novel molecular mechansims of tertiary resistance to third generation EGFR TKIs. An understanding of the mechanisms of acquired resistance to the third-generation EGFR TKIs will greatly aid in the development of the next generation of EGFR TKIs.

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Authors: Tan, C.-S., Cho, B.-C., & Soo, R. A.
Affiliations: National University Cancer Institute, Singapore (SG)
Yonsei Cancer Hospital (KR)
National University of Singapore (SG)
Corresponding author: Soo, Ross A.
ORCID: Tan, Chee-Seng
Cho, Byoung-Chul
Soo, Ross A.
Venue: Lung Cancer
Publisher: Elsevier BV
Published: 2016-03
Volume: 93
Pages: 59-68
ISSN: 0169-5002 (ISSN-L)
DOI: 10.1016/j.lungcan.2016.01.003
OpenAlex: W2230139348
Cited by: 105
References: 64
Citations by year: 2026: 2 · 2025: 3 · 2024: 2 · 2023: 4 · 2022: 3 · 2021: 8 · 2020: 9 · 2019: 13 · 2018: 10 · 2017: 33 · 2016: 18
FWCI: 4.28
Type: journal article
Language: en
Open access: green
ir.ymlib.yonsei.ac.kr
Licence: cc-by-nc-nd
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Lung Cancer (publishedVersion)
PubMed (publishedVersion)
UWA Profiles and Research Repository (UWA) (submittedVersion)
YUHSpace (Yonsei University Medical Library) (submittedVersion, cc-by-nc-nd)
Funders: National Research Foundation Singapore
Ministry of Education - Singapore
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 tyrosine kinase inhibitors, EGFR-mutant non-small cell lung cancer, third-generation EGFR-TKI, osimertinib, rociletinib, T790M mutation, acquired drug resistance, C797S mutation, plasma circulating tumor DNA, brain metastases, leptomeningeal metastasis, targeted therapy
MeSH terms: Animals, Antineoplastic Agents, Antineoplastic Combined Chemotherapy Protocols, Blood-Brain Barrier, Carcinoma, Non-Small-Cell Lung, Clinical Trials as Topic, Drug Evaluation, Preclinical, Humans, Lung Neoplasms, Mutation, Treatment Outcome, Protein Kinase Inhibitors, Drug Discovery, Molecular Targeted Therapy, ErbB Receptors

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Next-generation epidermal growth factor receptor tyrosine kinase inhibitors in epidermal growth factor receptor -mutant non-small cell lung cancer

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