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Topic: Cancer Stem Cells: Impact on Treatment

Therapeutic strategies for targeting cancer stem cells

Yu Jeong Kim , Elizabeth L. Siegler , Natnaree Siriwon , Pin Wang 1,2,3
2#
1#
3
1 Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90089, USA.
2 Department of Biomedical Engineering, University of Southern California, Los Angeles, CA 90089, USA.
3 Mork Family Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, CA 90089, USA.
# Authors contributed equally to this work
Correspondence to: Dr. Pin Wang, Mork Family Department of Chemical Engineering and Materials Science, University of Southern California, 3710
McClintock Ave, RTH509, Los Angeles, CA 90089, USA. E-mail: pinwang@usc.edu

Dr. Yu Jeong Kim is a PhD candidate in the Department of Pharmacology and Pharmaceutical Science at University
of Southern California (USC) mentored by Dr. Pin Wang. Her research focuses on liposomal nanoparticle-based drug
delivery for combination therapy such as co-delivering two inhibitors to target two distinct populations within tumor
bulk. Current studies involve the combination of immunotherapy and existing chemotherapeutic drug by utilizing
Chimeric Antigen Receptor (CAR)-engineered T cells and Natural Killer (NK) cells and pharmaceutical drugs loaded
crosslinked multilayer liposome vesicles for targeted cancer therapy.

A B S T R AC T
The therapeutic limitations of conventional chemotherapeutic drugs present a challenge for cancer therapy; these shortcomings
are largely attributed to the ability of cancer cells to repopulate and metastasize after initial therapies. Compelling evidence
suggests that cancer stem cells (CSCs) have a crucial impact in current shortcomings of cancer therapy because they are largely
responsible for tumor initiation, relapse, metastasis, and chemo-resistance. Thus, a better understanding of the properties and
mechanisms underlying CSC resistance to treatments is necessary to improve patient outcomes and survival rates. In this review,
the authors characterize and compare different CSC-specific biomarkers that are present in various types of tumors. We further
discuss multiple targeting approaches currently in preclinical or clinical testing that show great potential for targeting CSCs. This
review discusses numerous strategies to eliminate CSCs by targeting surface biomarkers, regulating CSC-associated oncogenes
and signaling pathways, inhibiting drug-efflux pumps involved in drug resistance, modulating the tumor microenvironment and
immune system, and applying drug combination therapy using nanomedicine.

Key words: Cancer stem cells; targeted cancer therapy; drug resistance

INTRODUCTION exists among tumor cells, with CSCs at the top, producing
the bulk of the tumor cells while maintaining their own
Cancer stem cells (CSCs) are a small subset of cancer cells renewal. A third model, clonal evolution, states that
[5]
with the ability to self-renew and initiate tumor growth. heterogeneity comes from genetic or epigenetic changes
They were first discovered in acute myeloid leukemia that arise during cancer progression. The CSC and clonal
(AML) in the late 1990s. Since then, CSCs have been evolution models are not mutually exclusive, as CSCs
[1]
discovered in many solid tumors. [2-6] Within the last two can also evolve over time, generating different clonal
decades, CSCs have become a subject of intense research subpopulations within the tumor. [6]
as a potential target for cancer therapeutics.
CSCs share a number of properties with normal stem
The discovery of CSCs led to a major shift in cancer cells (SCs). Both typically make up a small percentage
modeling. Previously, cancers were thought to be made of the total number of cells in a tissue, they are largely
up of equipotent malignant cells which either renewed or quiescent, and, most notably, they are multipotent and
differentiated stochastically, giving rise to a heterogeneous
tumor. In contrast, the CSC model suggests that a hierarchy This is an open access article distributed under the terms of the Creative
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How to cite this article: Kim YJ, Siegler EL, Siriwon N, Wang P.
Therapeutic strategies for targeting cancer stem cells. J Cancer
DOI: Metasta Treat 2016;2:233-42.
10.20517/2394-4722.2016.26
Received: 20-05-2016; Accepted: 21-06-2016.

©2016 Journal of Cancer Metastasis and Treatment ¦ Published by OAE Publishing Inc. 233