The challenge of targeting cancer stem cells to halt metastasis.
Despite a continuing debate about the existence of cancer stem cells (CSCs), recent discoveries have provided further support for their existence and their roles in drug resistance, cancer recurrence and metastasis. CSC characteristics, such as self-renewal and tumour initiation, and supporting cellular processes, particularly the epithelial-to-mesenchymal transition, are attracting a great deal of attention from cancer researchers as they offer opportunities for discovering novel therapeutic targets for future drug development. However, the identification of potential CSC targets presents clear obstacles due to a lack of truly specific CSC markers and the reality of CSC plasticity, making this task a significant challenge. Agents that target developmental signalling pathways, such as Notch, Wnt and Hedgehog, are now in clinical trials whilst alternative approaches including immune-based therapies and microRNA-mediated pathway inhibitors are producing promising pre-clinical results. Here, we discuss the contribution of CSCs to cancer metastasis and the scope of opportunities for therapeutic intervention. In particular, we consider CSC-targeting agents for which there is experimental evidence of anti-metastatic properties and which may have potential to eventually limit relapse and impede metastasis in patients.
Cancer Research UK Cancer Imaging Centre, Division of Radiotherapy and Imaging, The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, 123 Old Brompton Road, London, SW7 3RP, United Kingdom. Electronic address: Alice.Agliano@icr.ac.uk.
Alice
A
Agliano
CIBERONC/IDISNA Program of Solid Tumours and Biomarkers, CIMA of the University of Navarra and Department of Histology and Pathology, School of Medicine, University of Navarra, Pamplona, Spain. Electronic address: acalvo@unav.es.
Alfonso
A
Calvo
Cancer Research UK Cancer Imaging Centre, Division of Radiotherapy and Imaging, The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, 123 Old Brompton Road, London, SW7 3RP, United Kingdom. Electronic address: Carol.Box@icr.ac.uk.
Carol
C
Box
D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D006801:Humans; D035683:MicroRNAs / Q000235:genetics; D058990:Molecular Targeted Therapy; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects
D035683:MicroRNAs
Cancer stem cell; Epithelial-to-mesenchymal transition; Metastasis; Microenvironment; Therapy resistance