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Lung Neuroendocrine Tumors: How Does Molecular Profiling Help?
Thomas Yang Sun1, Andrew Hendifar2, Sukhmani K Padda3
1Department of Medicine, Division of Oncology, Stanford University School of Medicine, 875 Blake Wilbur Drive, Stanford, CA, USA.
Purpose Of Review:
Lung neuroendocrine tumors (NETs)-typical carcinoids and atypical carcinoids-have unique molecular alterations that are distinct from neuroendocrine carcinomas of the lung and non-small cell lung cancers. Here, we review the role of molecular profiling in the prognosis and treatment of lung NETs.
Recent Findings:
There have been no recently identified molecular prognostic factors for lung NETs and none that have been routinely used to guide management of patients with lung NETs. Previous findings suggest that patients with loss of chromosome 11q may have a worse prognosis along with upregulation of anti-apoptotic pathways (e.g., loss of CD44 and OTP protein expression). Lung NETs rarely harbor driver mutations commonly found in non-small cell lung cancer (NSCLC) or TP53/RB1 mutations found universally in small cell lung cancer. Lung NETs also have low tumor mutation burden and low PD-L1 expression. Everolimus, an mTOR inhibitor and the only FDA approved therapy for unresectable lung NETs, is an effective treatment but the presence of a molecular alteration in the PI3K/AKT/mTOR pathway is not known to predict treatment response. The predominant mutations in lung NETs occur in genes regulating chromatin remodeling and histone modification, with potential targeted therapies emerging in clinical trials. Lung NETs have recurring alterations in genes that regulate the epigenome. Future targeted therapy interfering with epigenetic pathways may hold promise.
Insights
Molecular profiling reveals unique alterations in lung neuroendocrine tumors (NETs). While current treatments like everolimus are effective, targeting epigenetic pathways offers promising future therapeutic strategies for lung NETs.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Lung neuroendocrine tumors (NETs) possess distinct molecular profiles compared to other lung cancers.
- Understanding these unique alterations is crucial for improving patient prognosis and treatment strategies.
Purpose of the Study:
- To review the role of molecular profiling in the prognosis and treatment of lung NETs.
- To highlight unique molecular alterations in lung NETs and their implications for targeted therapies.
Main Methods:
- Review of existing literature on molecular profiling of lung NETs.
- Analysis of genetic mutations, epigenetic alterations, and their correlation with prognosis and treatment response.
Main Results:
- Lung NETs show unique molecular alterations, differing from non-small cell lung cancer and other neuroendocrine carcinomas.
- No routine molecular prognostic factors are currently established for lung NETs.
- Predominant mutations involve chromatin remodeling and histone modification genes, suggesting epigenetic pathway dysregulation.
- Low tumor mutation burden and PD-L1 expression are characteristic of lung NETs.
- Everolimus is an effective treatment, but its response is not predicted by PI3K/AKT/mTOR pathway alterations.
Conclusions:
- Lung NETs have recurring epigenetic alterations that present potential targets for novel therapies.
- Future research should focus on developing targeted therapies that interfere with these epigenetic pathways.
- Molecular profiling is key to understanding lung NETs and advancing personalized treatment approaches.
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