Related Experiment Video
Updated: Oct 8, 2025
Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
HER2 Aberrations in Non-Small Cell Lung Cancer: From Pathophysiology to Targeted Therapy
Ioannis A Vathiotis1,2, Andriani Charpidou1, Niki Gavrielatou2
1Section of Medical Oncology, Third Department of Internal Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece.
Abstract:
While human epidermal growth factor receptor 2 (HER2) aberrations have long been described in patients with non-small cell lung cancer (NSCLC), they have only recently been effectively targeted. Unlike patients with breast cancer, NSCLC patients can harbor either HER2-activating mutations or HER2 amplification coupled with protein overexpression. The latter has also been the case for patients with acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). As preclinical data continue to accumulate, clinical trials evaluating novel agents that target HER2 have produced promising preliminary results. Here, we review existing data on HER2 aberrations in NSCLC. Starting from HER2 biology in normal and disease processes, we summarize discrepancies in HER2 diagnostic assays between breast cancer and NSCLC. Finally, to dissect the therapeutic implications of HER2-activating mutations versus gene amplification and/or protein overexpression, we present data from prospective clinical trials that have employed distinct classes of agents to target HER2 in patients with NSCLC.
Insights
Human epidermal growth factor receptor 2 (HER2) aberrations are increasingly targeted in non-small cell lung cancer (NSCLC). This review covers HER2 biology, diagnostics, and clinical trials for HER2-mutated or amplified NSCLC.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Human epidermal growth factor receptor 2 (HER2) aberrations, including activating mutations and gene amplification with protein overexpression, are recognized in non-small cell lung cancer (NSCLC).
- HER2 aberrations in NSCLC differ from breast cancer, presenting unique diagnostic and therapeutic challenges.
- Acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) can involve HER2 alterations in NSCLC.
Purpose of the Study:
- To review the current understanding of HER2 biology and its aberrations in NSCLC.
- To summarize discrepancies in HER2 diagnostic assays between breast cancer and NSCLC.
- To analyze the therapeutic implications of distinct HER2 aberration types in NSCLC through clinical trial data.
Main Methods:
- Review of existing literature on HER2 aberrations in NSCLC.
- Analysis of HER2 biology in normal and disease states.
- Comparison of diagnostic assay methodologies for HER2 in different cancer types.
- Evaluation of prospective clinical trial data for HER2-targeted agents in NSCLC.
Main Results:
- NSCLC patients can exhibit HER2-activating mutations or HER2 amplification with overexpression, unlike breast cancer patients.
- Preliminary results from clinical trials targeting HER2 in NSCLC show promise.
- Discrepancies exist in HER2 diagnostic assays between breast cancer and NSCLC, impacting treatment decisions.
Conclusions:
- Targeting HER2 in NSCLC is a rapidly evolving field with promising therapeutic strategies.
- Understanding the specific type of HER2 aberration (mutation vs. amplification/overexpression) is crucial for effective treatment selection in NSCLC.
- Further clinical trials are essential to optimize HER2-targeted therapies for NSCLC patients.
More Related Videos
08:59Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down
Published on: December 11, 2017
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
02:23Abnormal Proliferation
02:49Cancer Therapies
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
02:07Tumor Progression
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...