Lung Neuroendocrine Tumors: How Does Molecular Profiling Help?

Thomas Yang Sun, Andrew Hendifar, Sukhmani K. Padda

Research output: Contribution to journalReview articlepeer-review

4 Scopus citations

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.

Original languageEnglish
Pages (from-to)819-824
Number of pages6
JournalCurrent Oncology Reports
Volume24
Issue number7
DOIs
StatePublished - Jul 2022

Keywords

  • Atypical carcinoid
  • DIPNECH
  • Epigenetics
  • Everolimus
  • Genetics
  • Genomics
  • Histone
  • Lung neuroendocrine tumor
  • MEN1
  • Methylation
  • Molecular profiling
  • NETs
  • Neuroendocrine tumor
  • Prognosis
  • Sequencing
  • Targeted therapies
  • Treatment
  • Typical carcinoid
  • mTOR

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