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Lung Neuroendocrine Tumors: How Does Molecular Profiling Help?

  • Neuroendocrine Neoplasms (NS Reed, Section Editor)
  • Published:
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Abstract

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.

Summary

Lung NETs have recurring alterations in genes that regulate the epigenome. Future targeted therapy interfering with epigenetic pathways may hold promise.

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Authors and Affiliations

  1. Department of Medicine, Division of Oncology, Stanford University School of Medicine, 875 Blake Wilbur Drive, Stanford, CA, USA

    Thomas Yang Sun

  2. Department of Medicine, Division of Oncology, Cedars-Sinai Medical Center, 127 S San Vicente Blvd, 7th Floor, Los Angeles, CA, USA

    Andrew Hendifar & Sukhmani K. Padda

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  1. Thomas Yang Sun
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Correspondence to Sukhmani K. Padda.

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TYS and SKP declare no conflict of interest. AH is a consultant for Ipsen and Novartis.

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Sun, T.Y., Hendifar, A. & Padda, S.K. Lung Neuroendocrine Tumors: How Does Molecular Profiling Help?. Curr Oncol Rep 24, 819–824 (2022). https://doi.org/10.1007/s11912-022-01253-9

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