title: Cancer Stem Cell Hypothesis for Therapeutic Innovation in Clinical Oncology? Taking the Root Out, Not Chopping the Leaf.
abstract: Clinical oncology is in need of therapeutic innovation. New hypotheses and concepts for translation of basic research to novel diagnostics and therapeutics are called for. In this context, the cancer stem cell (CSC) hypothesis rests on the premise that tumors comprise tumor cells and a subset of tumor-initiating cells, CSCs, in a quiescent state characterized by slow cell cycling and expression of specific stem cell surface markers with the capability to maintain a tumor in vivo. The CSCs have unlimited self-renewal abilities and propagate tumors through division into asymmetric daughter cells. This differentiation is induced by both genetic and environmental factors. Another characteristic of CSCs is their therapeutic resistance, which is due to their quiescent state and slow dividing. Notably, the CSC phenotype differs greatly between patients and different cancer types. The CSCs may differ genetically and phenotypically and may include primary CSCs and metastatic stem cells circulating within the blood system. Targeting CSCs will require the knowledge of distinct stem cells within the tumor. CSCs can differentiate into nontumorigenic cells and this has been touted as the source of heterogeneity observed in many solid tumors. The latter cannot be fully explained by epigenetic regulation or by the clonal evolution theory. This heterogeneity markedly influences how tumors respond to therapy and prognosis. The present expert review offers an analysis and synthesis of the latest research and concepts on CSCs, with a view to truly disruptive innovation for future diagnostics and therapeutics in clinical oncology.
authors.affiliation: 1 International Centre for Genetic Engineering and Biotechnology (ICGEB) , Cape Town Component, Wernher and Beit Building (South), UCT Medical Campus, Anzio Road, Observatory 7925, Cape Town, South Africa .|2 Division of Medical Biochemistry and Institute of Infectious Disease and Molecular Medicine, Department of Integrative Biomedical Sciences, Faculty of Health Sciences, University of Cape Town , Cape Town, South Africa .
authors.forename: Kevin
authors.initials: K
authors.lastname: Dzobo
authors.affiliation: 1 International Centre for Genetic Engineering and Biotechnology (ICGEB) , Cape Town Component, Wernher and Beit Building (South), UCT Medical Campus, Anzio Road, Observatory 7925, Cape Town, South Africa .|2 Division of Medical Biochemistry and Institute of Infectious Disease and Molecular Medicine, Department of Integrative Biomedical Sciences, Faculty of Health Sciences, University of Cape Town , Cape Town, South Africa .
authors.forename: Dimakatso Alice
authors.initials: DA
authors.lastname: Senthebane
authors.affiliation: 1 International Centre for Genetic Engineering and Biotechnology (ICGEB) , Cape Town Component, Wernher and Beit Building (South), UCT Medical Campus, Anzio Road, Observatory 7925, Cape Town, South Africa .|2 Division of Medical Biochemistry and Institute of Infectious Disease and Molecular Medicine, Department of Integrative Biomedical Sciences, Faculty of Health Sciences, University of Cape Town , Cape Town, South Africa .
authors.forename: Arielle
authors.initials: A
authors.lastname: Rowe
authors.affiliation: 3 Pharmacogenetics Research Group, Division of Human Genetics, Department of Pathology and Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town , South Africa .
authors.forename: Nicholas Ekow
authors.initials: NE
authors.lastname: Thomford
authors.affiliation: 1 International Centre for Genetic Engineering and Biotechnology (ICGEB) , Cape Town Component, Wernher and Beit Building (South), UCT Medical Campus, Anzio Road, Observatory 7925, Cape Town, South Africa .|2 Division of Medical Biochemistry and Institute of Infectious Disease and Molecular Medicine, Department of Integrative Biomedical Sciences, Faculty of Health Sciences, University of Cape Town , Cape Town, South Africa .
authors.forename: Lamech M
authors.initials: LM
authors.lastname: Mwapagha
authors.affiliation: 4 Department of Clinical Pharmacy, Faculty of Clinical Pharmacy, Albaha University , Albaha, Saudi Arabia .
authors.forename: Nasir
authors.initials: N
authors.lastname: Al-Awwad
authors.affiliation: 3 Pharmacogenetics Research Group, Division of Human Genetics, Department of Pathology and Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town , South Africa .
authors.forename: Collet
authors.initials: C
authors.lastname: Dandara
authors.affiliation: 1 International Centre for Genetic Engineering and Biotechnology (ICGEB) , Cape Town Component, Wernher and Beit Building (South), UCT Medical Campus, Anzio Road, Observatory 7925, Cape Town, South Africa .|2 Division of Medical Biochemistry and Institute of Infectious Disease and Molecular Medicine, Department of Integrative Biomedical Sciences, Faculty of Health Sciences, University of Cape Town , Cape Town, South Africa .
authors.forename: M Iqbal
authors.initials: MI
authors.lastname: Parker
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D006801:Humans; D008495:Medical Oncology / Q000379:methods*; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor
keywords: biomarkers; cancer stem cells; disruptive innovation; heterogeneity; innovation systems; stem cell markers; therapeutics; tumour initiating cells