Dean M, Fojo T, Bates S.. Tumor stem cells and drug resistance. Nat Rev Cancer 5: 275-284

Laboratory of Genomic Diversity, National Cancer Institute-Frederick, Frederick, Maryland 21702, USA.
Nature reviews. Cancer (Impact Factor: 37.4). 05/2005; 5(4):275-84. DOI: 10.1038/nrc1590
Source: PubMed

ABSTRACT The contribution of tumorigenic stem cells to haematopoietic cancers has been established for some time, and cells possessing stem-cell properties have been described in several solid tumours. Although chemotherapy kills most cells in a tumour, it is believed to leave tumour stem cells behind, which might be an important mechanism of resistance. For example, the ATP-binding cassette (ABC) drug transporters have been shown to protect cancer stem cells from chemotherapeutic agents. Gaining a better insight into the mechanisms of stem-cell resistance to chemotherapy might therefore lead to new therapeutic targets and better anticancer strategies.

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    • "Their poor selectivity leads to severe systemic side effects, including multidrug resistance [4]. To circumvent the limitations associated with nonselective chemotherapeutics, researchers have developed 'smart' drug delivery systems (DDS) with a specific responsiveness to different stimuli [5- 10]. "
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    ABSTRACT: Nanomedicine seeks to apply nanoscale materials for the therapeutic and diagnostic purposes of diseased and damaged tissues. Recent advances in nanotechnology have made a major contribution to the development of multifunctional nanomaterials, which represents a paradigm shift from single purpose to multipurpose materials. Multifunctional nanomaterials have been proposed to enable simultaneous target imaging and on-demand delivery therapeutic agents only to the specific site [1]. Most advanced systems are also responsive to internal or external stimuli. This approach is particularly important for highly potent drugs (e.g. chemotherapeutics), which should be delivered in discreet manner, and interact with cells / tissues locally only. Both advances in imaging and precisely controlled and localized delivery are critically important in cancer treatment, and the use of such systems – theranostics – holds great promise to significantly reduce severe side effects of the dreary treatment whilst boosting the treatment effectiveness. Among others, mesoporous silica nanoparticles (MSNPs) are considered one of the most promising nanomaterials for drug delivery. Due to their unique intrinsic features, including tunable porosity and size, large surface area, structural diversity, easily modifiable chemistry and suitability for functionalization, and biocompatibility, MSNPs have been extensively utilized as multifunctional nanocarrier systems. The combination or hybridization with biomolecules, drugs, and other nanoparticles potentiated the ability of MSNPs towards multifunctionality, and even smart actions stimulated by specified signals, including pH, optical signal, redox reaction, electricity and magnetism. This paper provides the comprehensive review of state-of-art of multifunctional, smart drug delivery systems centered on advanced MSNPs, with special emphasis on cancer related applications.
    Nanoscale 07/2015; 7(34). DOI:10.1039/C5NR02730F · 7.39 Impact Factor
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    • "Because of their longevity in the tissue, normal stem cells are endowed with increased xenobiotic resistance, in part, due to the expression of efflux pumps (Zhou et al, 2001; Challen and Little, 2006; Kenyon and Gerson, 2007; DeNicola et al, 2011; Nakasone et al, 2012; Rosenzweig, 2012), more efficient DNA repair (Kenyon and Gerson, 2007) and they also orchestrate tissue changes during wound healing. Thus, the stem-like state is deeply linked to resilience and stress response – a relationship that appears to hold for their neoplastic counterpart, the cancer stem cells (CSC) (Dean et al, 2005; Donnenberg and Donnenberg, 2005; Medema, 2013). A fundamental biological fact is then that the axis of cell phenotype with respect to drug tolerance is aligned with that of cellular stemness. "
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    ABSTRACT: Therapy resistance and tumour relapse after drug therapy are commonly explained by Darwinian selection of pre-existing drug-resistant, often stem-like cancer cells resulting from random mutations. However, the ubiquitous non-genetic heterogeneity and plasticity of tumour cell phenotype raises the question: are mutations really necessary and sufficient to promote cell phenotype changes during tumour progression? Cancer therapy inevitably spares some cancer cells, even in the absence of resistant mutants. Accumulating observations suggest that the non-killed, residual tumour cells actively acquire a new phenotype simply by exploiting their developmental potential. These surviving cells are stressed by the cytotoxic treatment, and owing to phenotype plasticity, exhibit a variety of responses. Some are pushed into nearby, latent attractor states of the gene regulatory network which resemble evolutionary ancient or early developmental gene expression programs that confer stemness and resilience. By entering such stem-like, stress-response states, the surviving cells strengthen their capacity to cope with future noxious agents. Considering non-genetic cell state dynamics and the relative ease with which surviving but stressed cells can be tipped into latent attractors provides a foundation for exploring new therapeutic approaches that seek not only to kill cancer cells but also to avoid promoting resistance and relapse that are inherently linked to the attempts to kill them.British Journal of Cancer advance online publication 12 May 2015. doi:10.1038/bjc.2015.146
    British Journal of Cancer 05/2015; 112(11). DOI:10.1038/bjc.2015.146 · 4.84 Impact Factor
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    • "In recent years, an increasing body of evidence points to the existence of a cell subpopulation with low differentiation, called cancer stem cells (CSCs) [1]. These cells differ from other populations of the tumor in the presence of stem cell markers [2], and have specific characteristics, such as resistance to traditional chemotherapy and radiotherapy [3], apart from the capacity for self-renewal, being able to initiate the development of a new tumor [4]. "
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    ABSTRACT: Cancer stem cells (CSCs) comprise a tumor subpopulation responsible for tumor maintenance, resistance to chemotherapy, recurrence and metastasis. The identification of this cell group is very important, but there is still no consensus on its characterization. Several CSC markers have been described, like CD133, CD24, CD44 and ALDH1, but more research to identify new markers to facilitate the identification of CSC in a heterogeneous tumoral mass is required. Thus, this article describes the CD26 expression as a CSC marker and the role that it plays in different types of cancer. CD26 expression correlates with some characteristics of CSCs, like the formation of spheres in vitro, formation of new tumors, and resistance to chemotherapy. CD26 is therefore suggested as an auxiliary marker for CSC in different types of cancer, and as a potential therapeutic target. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
    Biomedecine [?] Pharmacotherapy 03/2015; 71. DOI:10.1016/j.biopha.2015.02.031 · 2.02 Impact Factor
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