Targeting HER2 in the treatment of non-small cell lung cancer
Nataliya Mar1, James J Vredenburgh2, Jeffrey S Wasser1
1University of Connecticut Health Center, Department of Hematology/Oncology, United States.
Abstract:
Oncogenic driver mutations have emerged as major treatment targets for molecular therapies in a variety of cancers. HER2 positivity has been well-studied in breast cancer, but its importance is still being explored in non-small cell lung cancer (NSCLC). Laboratory methods for assessment of HER2 positivity in NSCLC include immunohistochemistry (IHC) for protein overexpression, fluorescent in situ hybridization (FISH) for gene amplification, and next generation sequencing (NGS) for gene mutations. The prognostic and predictive significance of these tests remain to be validated, with an emerging association between HER2 gene mutations and response to HER2 targeted therapies. Despite the assay used to determine the HER2 status of lung tumors, all patients with advanced HER2 positive lung adenocarcinoma should be evaluated for treatment with targeted agents. Several clinical approaches for inclusion of these drugs into patient treatment plans exist, but there is no defined algorithm specific to NSCLC.
Insights
HER2 positivity is increasingly important in non-small cell lung cancer (NSCLC). Patients with advanced HER2-positive lung adenocarcinoma should be considered for targeted therapies, regardless of the testing method used.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Oncogenic driver mutations are key targets for cancer molecular therapies.
- HER2 (Human Epidermal growth factor Receptor 2) positivity is well-established in breast cancer, with growing interest in non-small cell lung cancer (NSCLC).
Purpose of the Study:
- To explore the significance of HER2 positivity in NSCLC.
- To review laboratory methods for assessing HER2 status in NSCLC.
- To highlight the emerging association between HER2 gene mutations and targeted therapy response.
Main Methods:
- Immunohistochemistry (IHC) for protein overexpression.
- Fluorescent in situ hybridization (FISH) for gene amplification.
- Next-generation sequencing (NGS) for gene mutations.
Main Results:
- The prognostic and predictive significance of HER2 testing in NSCLC requires further validation.
- An association between HER2 gene mutations and response to HER2-targeted therapies is emerging.
- All patients with advanced HER2-positive lung adenocarcinoma warrant evaluation for targeted agent treatment.
Conclusions:
- HER2 status is an important consideration in advanced NSCLC.
- Targeted therapies should be evaluated for HER2-positive lung adenocarcinoma patients.
- A defined treatment algorithm for HER2-positive NSCLC is currently lacking.
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