Case report: Personalized management of treatment resistance in advanced NSCLC patients with mutated epidermal growth factor receptor: special examples and literature review

The treatment landscape of non-small cell lung cancer (NSCLC) has shifted significantly from empirical, histology-driven, and clinician-directed cytotoxic regimens to a stratified approach predicated on molecular profiling of tumor genetics and immune biomarkers, by the former can indicate targeted...

Full description

Saved in:
Bibliographic Details
Main Authors: Jun Wang, Xiaojing Li, Shuang Dong, Sheng Hu, Fengming Ran, Yu Qian
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-02-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2025.1525881/full
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1823861108184711168
author Jun Wang
Jun Wang
Xiaojing Li
Shuang Dong
Sheng Hu
Fengming Ran
Yu Qian
author_facet Jun Wang
Jun Wang
Xiaojing Li
Shuang Dong
Sheng Hu
Fengming Ran
Yu Qian
author_sort Jun Wang
collection DOAJ
description The treatment landscape of non-small cell lung cancer (NSCLC) has shifted significantly from empirical, histology-driven, and clinician-directed cytotoxic regimens to a stratified approach predicated on molecular profiling of tumor genetics and immune biomarkers, by the former can indicate targeted therapy that bull’s eye hits the arrow, while the latter can hint the benefit amplitude of immune checkpoint inhibitors (ICBs). While third-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) have become the cornerstone of frontline therapy for patients harboring classic sensitive EGFR mutations, all tumors ultimately develop acquired resistance to these approaches, which can be categorized into three primary mechanism subclasses. The first subclass involves the acquisition of target mutations that lead to changes in the kinase domain, thereby hindering drug binding. The second mechanism, known as bypass resistance, entails tumor clones utilizing alternative signaling pathways for proliferation. Lastly, the third acquired mechanism pertains to histological transformation, such as the emergence of small cell lung cancer (SCLC) clones. The transformation of pathological types has brought great confusion to the clinical diagnosis and treatment process. We report a case of advanced lung adenocarcinoma with EGFR-sensitive mutation that transformed into small cell lung cancer after EGFR-TKIs treatment. Subsequent treatment revealed the presence of both adenocarcinoma and small cell carcinoma through needle biopsies at various metastatic sites. Based on the pathological, the patient received combination therapy with anlotinib at different times and achieved a long survival time.
format Article
id doaj-art-7446c93674514438aabba092caa417a5
institution Kabale University
issn 2234-943X
language English
publishDate 2025-02-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Oncology
spelling doaj-art-7446c93674514438aabba092caa417a52025-02-10T05:16:13ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-02-011510.3389/fonc.2025.15258811525881Case report: Personalized management of treatment resistance in advanced NSCLC patients with mutated epidermal growth factor receptor: special examples and literature reviewJun Wang0Jun Wang1Xiaojing Li2Shuang Dong3Sheng Hu4Fengming Ran5Yu Qian6Department of Thoracic Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaLaboratory of Natural Medicine and Molecular Engineering, College of Plant Science and Technology, Huazhong Agricultural University, Wuhan, ChinaDepartment of Pharmacy, Puren Hospital, Wuhan University of Science and Technology, Wuhan, ChinaDepartment of Thoracic Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Thoracic Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Thoracic Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Thoracic Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaThe treatment landscape of non-small cell lung cancer (NSCLC) has shifted significantly from empirical, histology-driven, and clinician-directed cytotoxic regimens to a stratified approach predicated on molecular profiling of tumor genetics and immune biomarkers, by the former can indicate targeted therapy that bull’s eye hits the arrow, while the latter can hint the benefit amplitude of immune checkpoint inhibitors (ICBs). While third-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) have become the cornerstone of frontline therapy for patients harboring classic sensitive EGFR mutations, all tumors ultimately develop acquired resistance to these approaches, which can be categorized into three primary mechanism subclasses. The first subclass involves the acquisition of target mutations that lead to changes in the kinase domain, thereby hindering drug binding. The second mechanism, known as bypass resistance, entails tumor clones utilizing alternative signaling pathways for proliferation. Lastly, the third acquired mechanism pertains to histological transformation, such as the emergence of small cell lung cancer (SCLC) clones. The transformation of pathological types has brought great confusion to the clinical diagnosis and treatment process. We report a case of advanced lung adenocarcinoma with EGFR-sensitive mutation that transformed into small cell lung cancer after EGFR-TKIs treatment. Subsequent treatment revealed the presence of both adenocarcinoma and small cell carcinoma through needle biopsies at various metastatic sites. Based on the pathological, the patient received combination therapy with anlotinib at different times and achieved a long survival time.https://www.frontiersin.org/articles/10.3389/fonc.2025.1525881/fullanlotinibadenocarcinomaSCLC transformationTKIs resistancepersonalized management
spellingShingle Jun Wang
Jun Wang
Xiaojing Li
Shuang Dong
Sheng Hu
Fengming Ran
Yu Qian
Case report: Personalized management of treatment resistance in advanced NSCLC patients with mutated epidermal growth factor receptor: special examples and literature review
Frontiers in Oncology
anlotinib
adenocarcinoma
SCLC transformation
TKIs resistance
personalized management
title Case report: Personalized management of treatment resistance in advanced NSCLC patients with mutated epidermal growth factor receptor: special examples and literature review
title_full Case report: Personalized management of treatment resistance in advanced NSCLC patients with mutated epidermal growth factor receptor: special examples and literature review
title_fullStr Case report: Personalized management of treatment resistance in advanced NSCLC patients with mutated epidermal growth factor receptor: special examples and literature review
title_full_unstemmed Case report: Personalized management of treatment resistance in advanced NSCLC patients with mutated epidermal growth factor receptor: special examples and literature review
title_short Case report: Personalized management of treatment resistance in advanced NSCLC patients with mutated epidermal growth factor receptor: special examples and literature review
title_sort case report personalized management of treatment resistance in advanced nsclc patients with mutated epidermal growth factor receptor special examples and literature review
topic anlotinib
adenocarcinoma
SCLC transformation
TKIs resistance
personalized management
url https://www.frontiersin.org/articles/10.3389/fonc.2025.1525881/full
work_keys_str_mv AT junwang casereportpersonalizedmanagementoftreatmentresistanceinadvancednsclcpatientswithmutatedepidermalgrowthfactorreceptorspecialexamplesandliteraturereview
AT junwang casereportpersonalizedmanagementoftreatmentresistanceinadvancednsclcpatientswithmutatedepidermalgrowthfactorreceptorspecialexamplesandliteraturereview
AT xiaojingli casereportpersonalizedmanagementoftreatmentresistanceinadvancednsclcpatientswithmutatedepidermalgrowthfactorreceptorspecialexamplesandliteraturereview
AT shuangdong casereportpersonalizedmanagementoftreatmentresistanceinadvancednsclcpatientswithmutatedepidermalgrowthfactorreceptorspecialexamplesandliteraturereview
AT shenghu casereportpersonalizedmanagementoftreatmentresistanceinadvancednsclcpatientswithmutatedepidermalgrowthfactorreceptorspecialexamplesandliteraturereview
AT fengmingran casereportpersonalizedmanagementoftreatmentresistanceinadvancednsclcpatientswithmutatedepidermalgrowthfactorreceptorspecialexamplesandliteraturereview
AT yuqian casereportpersonalizedmanagementoftreatmentresistanceinadvancednsclcpatientswithmutatedepidermalgrowthfactorreceptorspecialexamplesandliteraturereview