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World J Stem Cells. Jan 26, 2016; 8(1): 13-21
Published online Jan 26, 2016. doi: 10.4252/wjsc.v8.i1.13
Targeting head and neck tumoral stem cells: From biological aspects to therapeutic perspectives
Benoîte Méry, Jean-Baptiste Guy, Sophie Espenel, Anne-Sophie Wozny, Stéphanie Simonet, Alexis Vallard, Gersende Alphonse, Dominique Ardail, Claire Rodriguez-Lafrasse, Nicolas Magné
Benoîte Méry, Jean-Baptiste Guy, Sophie Espenel, Alexis Vallard, Nicolas Magné, Department of Radiotherapy, Lucien Neuwirth Cancer Institute, 42271 Saint-Priest en Jarez, France
Benoîte Méry, Jean-Baptiste Guy, Anne-Sophie Wozny, Stéphanie Simonet, Gersende Alphonse, Dominique Ardail, Claire Rodriguez-Lafrasse, Nicolas Magné, Laboratoire de Radiobiologie Cellulaire et Moléculaire de Lyon Sud, Faculté de Médecine Lyon Sud, 69921 Oullins Cedex, France
Author contributions: All authors equally contributed to this paper with conception and design of the study, literature review and analysis, drafting and critical revision and editing, and final approval of the final version.
Conflict-of-interest statement: Authors declare they have no conflict of interest.
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: Nicolas Magné, MD, PhD, Department of Radiotherapy, Lucien Neuwirth Cancer Institute, 108 bis, Avenue Albert Raimond, BP 60008, 42271 Saint-Priest en Jarez, France. nicolas.magne@icloire.fr
Telephone: +33-4-77917434 Fax: +33-4-77917197
Received: August 25, 2015
Peer-review started: August 28, 2015
First decision: October 27, 2015
Revised: November 19, 2015
Accepted: December 13, 2015
Article in press: December 14, 2015
Published online: January 26, 2016
Abstract

Head and neck squamous cell cancer (HNSCC) is the sixth most common cancer in the world. Effective therapeutic modalities such as surgery, radiation, chemotherapy and combinations of each are used in the management of the disease. In most cases, treatment fails to obtain total cancer cure. In recent years, it appears that one of the key determinants of treatment failure may be the presence of cancer stem cells (CSCs) that escape currently available therapies. CSCs form a small portion of the total tumor burden but may play a disproportionately important role in determining outcomes. CSCs have stem features such as self-renewal, high migration capacity, drug resistance, high proliferation abilities. A large body of evidence points to the fact that CSCs are particularly resistant to radiotherapy and chemotherapy. In HNSCC, CSCs have been increasingly shown to have an integral role in tumor initiation, disease progression, metastasis and treatment resistance. In the light of such observations, the present review summarizes biological characteristics of CSCs in HNSCC, outlines targeted strategies for the successful eradication of CSCs in HNSCC including targeting the self-renewal controlling pathways, blocking epithelial mesenchymal transition, niche targeting, immunotherapy approaches and highlights the need to better understand CSCs biology for new treatments modalities.

Keywords: Biology, Head and neck neoplasms, Oral cancer, Neoplastic stem cells, Molecular targeted therapy, Radiation therapy, Chemotherapy

Core tip: The cancer stem cells (CSCs) theory offers an insight into why currently available therapies for head and neck cancer fail so often. Eradication of cancers may require the targeting and elimination of CSCs, especially for head and neck squamous cell cancer (HNSCC). This represents a challenge because many pathways, such as those involved in self-renewal, are shared by CSCs and their normal counterparts and might lead to major toxicities. Developing radio sensitizing strategies is investigated and appears to eliminate CSCs. Overcoming chemo resistance, radio resistance and immune evasion mechanisms of CSCs remains a cornerstone of novel adjuvant therapies specifically targeting CSCs in HNSCC.