Cancer stem cells as targets for cancer therapy: selected cancers as examples.
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.
Department Human Anatomy and Cell Science, University of Manitoba, Winnipeg, Canada.
Sabine
S
Hombach-Klonisch
Ted
T
Paranjothy
Emilia
E
Wiechec
Paola
P
Pocar
Tarek
T
Mustafa
Anja
A
Seifert
Christian
C
Zahl
Klaus Luis
KL
Gerlach
Katharina
K
Biermann
Klaus
K
Steger
Cuong
C
Hoang-Vu
Klaus
K
Schulze-Osthoff
Marek
M
Los
D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D005260:Female; D020869:Gene Expression Profiling; D006258:Head and Neck Neoplasms / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy; D006412:Hematopoietic Stem Cells / Q000502:physiology; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000502:physiology; D009062:Mouth Neoplasms / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000502:physiology*; D010051:Ovarian Neoplasms / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy; D015398:Signal Transduction; D013736:Testicular Neoplasms / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy
D014408:Biomarkers, Tumor