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Updated: Mar 9, 2026
Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Massive parallel sequencing and digital gene expression analysis reveals potential mechanisms to overcome therapy
Robert Fred Henry Walter1, Claudia Vollbrecht2, Daniel Christoph3
1Ruhrlandklinik, West German Lung Center, University Hospital Essen, University of Duisburg-Essen;; Institute of Pathology, Charité Universitaetsmedizin, Berlin.
Abstract:
Background: Lung cancer is the leading cause of cancer-related deaths worldwide. 25% show neuroendocrine differentiation (typical/atypical carcinoids, large-/small-cell neuroendocrine carcinomas). Carcinoids present with long survival rates, but metastatic carcinoids correlate with decreased survival and are commonly insensitive to standard chemotherapy or radiation. Therefore, novel therapeutic strategies are urgently needed. Material and methods: 70 representative tumor specimens were used for next-generation sequencing analysis of 14 genes related to therapy response. Additionally, mRNA-expression profiles of 60 matching samples were determined for 13 selected drug targets by using the NanoString nCounter technology. Results: A number of features known to sensitize tumors for different targeted therapies could be identified, which hopefully improve the clinical management of this subgroup of lung neoplasias. In particular, EGFR expression was observed in the investigated tumors in a noteworthy manner. Additionally, MDM2 was strongly expressed in the majority of all samples whereas the expression of its physiological inhibitor, CDKN2A, was nearly absent in all low-grade tumors. TP53 showed a high frequency of variants in high-grade tumors but mutations were rare in carcinoids. Conclusion: Based on our results, therapeutic approaches with MDM2-inhibitors and monoclonal anti-EGFR antibodies may be promising in pulmonary carcinoid tumors.
Insights
Novel therapies are needed for metastatic pulmonary carcinoid tumors. MDM2-inhibitors and anti-EGFR antibodies show promise, targeting key gene expressions like MDM2 and EGFR found in these rare lung cancers.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Lung cancer is a leading global cause of cancer mortality.
- Neuroendocrine differentiation is present in 25% of lung cancers, including carcinoids.
- Metastatic carcinoids have poor survival and are often resistant to conventional treatments, necessitating new therapeutic strategies.
Purpose of the Study:
- To investigate genetic and expression profiles of pulmonary carcinoid tumors.
- To identify potential therapeutic targets for improved clinical management.
- To evaluate the feasibility of targeted therapies in pulmonary carcinoid tumors.
Main Methods:
- Next-generation sequencing of 14 therapy-response genes in 70 tumor specimens.
- NanoString nCounter technology to determine mRNA expression of 13 drug targets in 60 samples.
- Analysis of gene expression and mutation profiles related to targeted therapies.
Main Results:
- Identified sensitizing features for targeted therapies in lung tumors.
- Noteworthy EGFR expression was observed in investigated tumors.
- Strong MDM2 expression was prevalent, while CDKN2A expression was low in low-grade tumors.
- TP53 variants were frequent in high-grade tumors but rare in carcinoids.
Conclusions:
- Therapeutic strategies involving MDM2-inhibitors may be beneficial for pulmonary carcinoid tumors.
- Monoclonal anti-EGFR antibodies could be a promising approach for treating these tumors.
- Targeted therapies based on identified molecular features offer potential for improved outcomes.
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