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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Oct 26, 2015; 7(9): 1185-1201
Published online Oct 26, 2015. doi: 10.4252/wjsc.v7.i9.1185
Therapies targeting cancer stem cells: Current trends and future challenges
Denisa L Dragu, Laura G Necula, Coralia Bleotu, Carmen C Diaconu, Mihaela Chivu-Economescu
Denisa L Dragu, Laura G Necula, Coralia Bleotu, Carmen C Diaconu, Mihaela Chivu-Economescu, Cellular and Molecular Department, Stefan S. Nicolau Institute of Virology, 030304 Bucharest, Romania
Laura G Necula, Nicolae Cajal Institute, Titu Maiorescu University, 004051 Bucharest, Romania
Laura G Necula, Biochemistry-Proteomics Department, Victor Babes National Institute of Pathology, 050096 Bucharest, Romania
Author contributions: Dragu DL wrote the sections on targeting microenvironment, manipulation of miRNA expression, induction of CSCs apoptosis and induction of CSCs differentiation; Necula LG wrote the section on targeting signal cascades; Bleotu C wrote the section on targeting surface markers; Diaconu CC wrote the section on targeting ABC transporters; Chivu-Economescu M wrote the introduction, the CSCs: definition, characteristics, markers section, conclusions and completed the integration of all sections in the final manuscript.
Supported by The European Social Fund; and the Romanian Government (Laura G Necula), No. POSDRU/159/1.5/S/137390.
Conflict-of-interest statement: Authors declare no conflict of interests for this article.
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: Mihaela Chivu-Economescu, PhD, Cellular and Molecular Department, Stefan S. Nicolau Institute of Virology, Mihai Bravu 285 Ave, 030304 Bucharest, Romania. mihaela.chivu@gmail.com
Telephone: +40-21-3242590 Fax: +40-21-3242590
Received: May 26, 2015
Peer-review started: May 28, 2015
First decision: July 3, 2015
Revised: August 2, 2015
Accepted: September 7, 2015
Article in press: September 8, 2015
Published online: October 26, 2015
Processing time: 156 Days and 17.7 Hours
Abstract

Traditional therapies against cancer, chemo- and radiotherapy, have multiple limitations that lead to treatment failure and cancer recurrence. These limitations are related to systemic and local toxicity, while treatment failure and cancer relapse are due to drug resistance and self-renewal, properties of a small population of tumor cells called cancer stem cells (CSCs). These cells are involved in cancer initiation, maintenance, metastasis and recurrence. Therefore, in order to develop efficient treatments that can induce a long-lasting clinical response preventing tumor relapse it is important to develop drugs that can specifically target and eliminate CSCs. Recent identification of surface markers and understanding of molecular feature associated with CSC phenotype helped with the design of effective treatments. In this review we discuss targeting surface biomarkers, signaling pathways that regulate CSCs self-renewal and differentiation, drug-efflux pumps involved in apoptosis resistance, microenvironmental signals that sustain CSCs growth, manipulation of miRNA expression, and induction of CSCs apoptosis and differentiation, with specific aim to hamper CSCs regeneration and cancer relapse. Some of these agents are under evaluation in preclinical and clinical studies, most of them for using in combination with traditional therapies. The combined therapy using conventional anticancer drugs with CSCs-targeting agents, may offer a promising strategy for management and eradication of different types of cancers.

Keywords: Cancer stem cells; Targeted therapy; Anticancer drugs; Biomarkers; Signaling pathways; Apoptosis

Core tip: Cancer stem cells (CSCs) play important roles in tumor formation, metastasis and cancer relapse. In this article, we review the literature on the recent progress in developing anti-cancer stem cell strategies based on improved understanding of CSCs properties and molecular features. These novel therapeutic systems are designed with the aim of eradicating CSCs, by targeting surface specific markers and altering signaling pathways or mechanisms involved in CSCs maintenance and drug resistance, and also to disturb microenvironmental signals that sustain CSCs growth, with specific aim of impede CSCs regeneration and cancer relapse.