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Cancer stem cells as targets for cancer therapy: selected cancers as examples

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Archivum Immunologiae et Therapiae Experimentalis Aims and scope

Abstract

It is becoming increasingly evident that cancer constitutes a group of diseases involving altered stem-cell maturation/differentiation and the disturbance of regenerative processes. The observed malignant transformation is merely a symptom of normal differentiation processes gone astray rather than the primary event. This review focuses on the role of cancer stem cells (CSCs) in three common but also relatively under-investigated cancers: head and neck, ovarian, and testicular cancer. For didactic purpose, the physiology of stem cells is first introduced using hematopoietic and mesenchymal stem cells as examples. This is followed by a discussion of the (possible) role of CSCs in head and neck, ovarian, and testicular cancer. Aside from basic information about the pathophysiology of these cancers, current research results focused on the discovery of molecular markers specific to these cancers are also discussed. The last part of the review is largely dedicated to signaling pathways active within various normal and CSC types (e.g. Nanog, Nestin, Notch1, Notch2, Oct3 and 4, Wnt). Different elements of these pathways are also discussed in the context of therapeutic opportunities for the development of targeted therapies aimed at CSCs. Finally, alternative targeted anticancer therapies arising from recently identified molecules with cancer-(semi-)selective capabilities (e.g. apoptin, Brevinin-2R) are considered.

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Abbreviations

BCC:

basal cell cancer

BM:

bone marrow

BMP:

bone morphogenetic protein

CHK2:

checkpoint kinase2

CSC:

cancer stem cell

CXCL12:

chemokine (C-X-C-motif) ligand 12

ES:

embryonic stem

Flk-1:

fetal liver kinase-1

GCT:

germ cell tumor

GPI:

guanyl phosphatidylinositol

HH/PTCH:

hedgehog/patched pathway

HSC:

hematopoietic stem cells

IGCNU:

intratubular germ cell neoplasia unclassified

KDR:

kinase insert domain-containing receptor

LRP5/6:

low-density lipoprotein receptor-related protein 5/6

MIS:

Müllerian inhibiting substance

MSC:

mesenchymal stem cell

OGCT:

ovarian GCT

OSCC:

oral squamous cell carcinoma

PGC:

primordial germ cell

ROS:

reactive oxygen species

Sca-1:

stem cell antigen-1

SCF-1:

stem cell factor-1

SHH:

sonic hedgehog

SMO:

smoothened

SP:

side population

STAT3:

signal transducer and activator of transcription 3

TGCT:

testicular GCTs

VEGFR2:

vascular endothelial growth factor receptor 2

VCAM:

vascular cell adhesion molecule

FCS:

fetal calf serum

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Authors and Affiliations

Authors

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Correspondence to Marek Los MD, Ph.D..

Additional information

Sabine Hombach-Klonisch, Ted Paranjothy: Shared first-authorship

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Hombach-Klonisch, S., Paranjothy, T., Wiechec, E. et al. Cancer stem cells as targets for cancer therapy: selected cancers as examples. Arch. Immunol. Ther. Exp. 56, 165–180 (2008). https://doi.org/10.1007/s00005-008-0023-4

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  • DOI: https://doi.org/10.1007/s00005-008-0023-4

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