Editorial
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Oncol. Dec 10, 2015; 6(6): 212-215
Published online Dec 10, 2015. doi: 10.5306/wjco.v6.i6.212
Combination therapies improve the anticancer activities of retinoids in neuroblastoma
Belamy B Cheung
Belamy B Cheung, Molecular Carcinogenesis Program, Children’s Cancer Institute, Lowy Cancer Research Centre, University of New South Wales, Sydney NSW 2031, Australia
Author contributions: Cheung BB solely contributed to this manuscript.
Conflict-of-interest statement: The author declares no conflicts of interest regarding this manuscript.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Belamy B Cheung, PhD, Molecular Carcinogenesis Program, Children’s Cancer Institute, Lowy Cancer Research Centre, University of New South Wales, PO Box 81, Randwick, Sydney NSW 2031, Australia. bcheung@ccia.unsw.edu.au
Telephone: +61-2-93852450 Fax: +61-2-96626584
Received: May 19, 2015
Peer-review started: May 20, 2015
First decision: August 4, 2015
Revised: September 10, 2015
Accepted: October 12, 2015
Article in press: October 13, 2015
Published online: December 10, 2015
Processing time: 204 Days and 6.7 Hours
Abstract

Most therapeutic protocols for child cancers use cytotoxic agents which have a narrow therapeutic index, and resulting in severe acute and chronic toxicities to normal tissues. Despite the fact that most child cancer patients achieve complete remission after chemotherapy, death still occurs due to relapse of persistent minimal residual disease (MRD) which remaining after initial cytotoxic chemotherapy. Advanced neuroblastoma (NB) is a leading cause of cancer deaths in young children. Retinoids are an important component of advanced NB therapy at the stage of MRD, yet half of all patients treated with 13-cis-retinoic acid still relapse and die. More effective combination therapies, with a lower side-effect profile, are required to improve outcomes for NB. Fenretinide or N-4-hydroxyphenyl retinamide is a synthetic derivative of retinoic acid which works on cancer cells through nuclear receptor-dependent and -independent signalling mechanisms. Moreover, several histone deacetylase inhibitors have entered early phase trials, and, suberoylanilide hydroxamic acid has been approved for use in adult cutaneous T cell lymphoma. A number of studies suggest that retinoid signal activation is necessary for histone deacetylase inhibitor activity. A better understanding of their mechanism of actions will lead to more evidence-based retinoid combination therapies.

Keywords: Retinoids, Histone deacetylase inhibitors, Combination therapies, Neuroblastoma, Fenretinide

Core tip: Neuroblastoma (NB) begins in embryonal neural crest cells, which later give rise to the sympathetic nervous system, and is caused in part by factors which arrest differentiation. In vitro, retinoids force susceptible cancer cells down a pathway of terminal differentiation and, have been part of the routine treatment of advanced NB for number of decades. Synergistic anti-tumour activity between histone deacetylase inhibitors and retinoids has been observed in a variety of preclinical models. This editorial note discusses some of these findings on the combination therapies for improving the anticancer activities of retinoids in NB.