Open Access

REVIEW

Histone deacetylase inhibitors as a novel therapeutic approach for pheochromocytomas and paragangliomas

by ASPASIA MANTA¹, SPYRIDON KAZANAS², STEFANOS KARAMAROUDIS³, HELEN GOGAS², DIMITRIOS C. ZIOGAS^2,*

1 Endocrine Unit, Second Department of Internal Medicine Propaedeutic & Research Institute, Medical School, National and Kapodistrian University of Athens, Attikon University Hospital, Athens, 12461, Greece
2 First Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, 11527, Greece
3 Department of Obstetrics & Gynecology, General Hospital of Elefsina Thriassio, Elefsina, 19600, Greece

* Corresponding Author: Dimitrios C. Ziogas,

Oncology Research 2022, 30(5), 211-219. https://doi.org/10.32604/or.2022.026913

Received 03 October 2022; Accepted 11 January 2023; Issue published 03 February 2023

Abstract

Epigenetic mechanisms, such as DNA methylation and histone modifications (e.g., acetylation and deacetylation), are strongly implicated in the carcinogenesis of various malignancies. During transcription, the expression and functionality of coding gene products are altered following the histone acetylation and deacetylation. These processes are regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs), respectively. HDAC inhibitors (HDACis) have been developed as promising therapeutic agents, to limit exposure to traditional and toxic chemotherapies and offer more alternatives for some specific malignant diseases with limited options. Mechanistically, these agents affect many intracellular pathways, including cell cycle arrest, apoptosis and differentiation, and their mechanism of action mainly depends on the type of cancer. Currently, five HDACis have been approved for the treatment of several hematological malignancies (e.g., T-cell lymphoma subtypes and multiple myeloma); while, many of them are tested for further therapeutic indications in solid tumors (e.g., colorectal, thyroid, breast, lung and pancreatic cancer). Herein, we review the literature and gather all available evidence, from in vitro and in vivo data to clinical trial results, that recognizes the antitumor activity of HDACis on pheochromocytomas and paragangliomas; and supports their clinical implementation in the treatment of these rare neuroendocrine tumors at metastatic setting.

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Keywords

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