Pulmonary carcinoid surface receptor modulation using histone deacetylase inhibitors

Rachael E. Guenter, Tolulope Aweda, Danilea M.Carmona Matos, Jason Whitt, Alexander W. Chang, Eric Y. Cheng, X. Margaret Liu, Herbert Chen, Suzanne E. Lapi, Renata Jaskula-Sztul

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Pulmonary carcinoids are a type of neuroendocrine tumor (NET) accounting for 1–2% of lung cancer cases. Currently, Positron Emission Tomography (PET)/CT based on the radiolabeled sugar analogue [18F]-FDG is used to diagnose and stage pulmonary carcinoids, but is suboptimal due to low metabolic activity in these tumors. A new technique for pulmonary carcinoid imaging, using PET/CT with radiolabeled somatostatin analogs that specifically target somatostatin receptor subtype 2 (SSTR2), is becoming more standard, as many tumors overexpress SSTR2. However, pulmonary carcinoid patients with diminished SSTR2 expression are not eligible for this imaging or any type of SSTR2-specific treatment. We have found that histone deacetylase (HDAC) inhibitors can upregulate the expression of SSTR2 in pulmonary carcinoid cell lines. In this study, we used a non-cytotoxic dose of HDAC inhibitors to induce pulmonary carcinoid SSTR2 expression in which we confirmed in vitro and in vivo. A non-cytotoxic dose of the HDAC inhibitors: Thailandepsin A (TDP-A), romidepsin (FK228), suberoylanilide hydroxamic acid (SAHA), AB3, and valproic acid (VPA) were administered to promote SSTR2 expression in pulmonary carcinoid cell lines and xenografts. This SSTR2 upregulation technique using HDAC inhibitors could enhance radiolabeled somatostatin analog-based imaging and the development of potential targeted treatments for pulmonary carcinoid patients with marginal or diminished SSTR2 expression.

Original languageEnglish
Article number767
JournalCancers
Volume11
Issue number6
DOIs
StatePublished - Jun 2019

Keywords

  • Histone deacetylase inhibitor
  • Neuroendocrine cancer
  • Pulmonary carcinoid
  • Somatostatin receptor

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