Related Experiment Video
Updated: Mar 7, 2026
Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure
Published on: August 11, 2017
ERBB2-Mutated Metastatic Non-Small Cell Lung Cancer: Response and Resistance to Targeted Therapies
Jody C Chuang1, Henning Stehr2, Ying Liang3
1Division of Hematology and Oncology, Stanford Hospital and Clinics, Stanford, California.
Introduction:
Erb-b2 receptor tyrosine kinase 2 gene (ERBB2) (also called HER2) has long been recognized as an oncogenic driver in some breast and gastroesophageal cancers in which amplification of this gene confers sensitivity to treatment with Erb-b2 receptor tyrosine kinase 2 (ERBB2)-directed agents. More recently, somatic mutations in ERBB2 have been reported in 1% to 2% of patients with lung adenocarcinoma. Previous case series have suggested clinical tumor responses using anti-ERBB2 small molecules and antibody therapies.
Methods:
Here we report the outcomes of nine patients with metastatic lung adenocarcinoma with ERBB2 mutations being treated with ERBB2-targeted therapies.
Results:
Four of the nine patients had response to targeted therapies, with durations of response ranging from 3 to 10 months. We identified a de novo phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha gene (PIK3CA) mutation and ERBB2 copy number gain as potential resistance mechanisms.
Conclusions:
We showed patients with ERBB2-mutated lung adenocarcinoma can respond to targeted therapies, and we identified potential resistance mechanisms upon progression to targeted therapies.
Insights
Lung adenocarcinoma patients with Erb-b2 receptor tyrosine kinase 2 (ERBB2) mutations showed responses to ERBB2-targeted therapies. Potential resistance mechanisms, including PIK3CA mutations, were identified.
Area of Science:
- Oncology
- Genetics
- Pharmacology
Background:
- The Erb-b2 receptor tyrosine kinase 2 (ERBB2) gene is an oncogenic driver in certain cancers, including breast and gastroesophageal cancers.
- ERBB2 amplification confers sensitivity to ERBB2-directed therapies in these cancers.
- Somatic mutations in ERBB2 have recently been identified in 1-2% of lung adenocarcinoma patients.
Purpose of the Study:
- To report the outcomes of patients with metastatic lung adenocarcinoma harboring ERBB2 mutations treated with ERBB2-targeted therapies.
- To investigate potential mechanisms of resistance to ERBB2-targeted therapies in this patient population.
Main Methods:
- Retrospective analysis of nine patients with metastatic lung adenocarcinoma and ERBB2 mutations.
- Treatment with ERBB2-targeted therapies.
Main Results:
- Four out of nine patients demonstrated a clinical response to ERBB2-targeted therapies.
- Response durations varied from 3 to 10 months.
- A de novo phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutation and ERBB2 copy number gain were identified as potential resistance mechanisms.
Conclusions:
- Patients with ERBB2-mutated lung adenocarcinoma can achieve responses with ERBB2-targeted therapies.
- Understanding resistance mechanisms is crucial for optimizing treatment strategies in ERBB2-mutated lung adenocarcinoma.
More Related Videos
09:38Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib
Published on: June 26, 2019
07:59Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:38Mitogens and the Cell Cycle
02:56Treatment Resistant Cancers
01:20The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
02:30Metastasis
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...