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Cancer stem cells: perspectives for therapeutic targeting

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Abstract

Cells with “stemness” and tumor-initiating properties have been isolated from both hematological and solid tumors. These cells denominated as cancer stem cells (CSCs), representing rare populations within tumors, have the ability to metastasize and are resistant to standard therapies and immunotherapy. Heterogeneity and plasticity in the phenotype of CSCs have been described in relation to their tissue origin. Few definitive markers have been isolated for CSCs from human solid tumors, limiting their usage for in vivo identification of these cells. Nevertheless, progress in the emerging CSCs concept has been achieved gaining, at least for some type of tumors, their biological and immunological characterization. The recent identification of molecules and signaling pathways that are up-regulated or aberrantly induced in CSCs allowed the development of small agents for specifically targeting of CSCs. A general low immunogenic profile has been reported for CSCs with, in some cases, the identification of the mechanisms responsible of the impairment of cell-mediated immune responses. These concepts are discussed in the context of this review. Although CSCs still need to be fully characterized, potential candidate markers and/or signaling pathways, to be exploited for the design of novel CSC-targeting therapeutic strategies, are described in this review.

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Abbreviations

ALDH:

Aldehyde dehydrogenase

BMP4:

Bone morphogenetic protein 4

COA-1:

Colon antigen-1

CRC:

Colorectal cancer

CSCs:

Cancer stem cells

DLL4:

Delta-like ligand 4

GDF-15:

Growth differentiation factor-15

GBM:

Glioblastoma multiforme

IFN:

Interferon

mAb:

Monoclonal antibody

MDR1:

Multi-drug resistance 1 gene

PD-1:

Programmed death 1

PGE2:

Prostaglandin E2

PI3K:

Phosphatidylinositide 3-kinase

PTEN:

Phosphatase and tensin homolog

TGFB-1:

Transforming growth factor beta 1

XIAP:

X-linked inhibitor of apoptosis

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  1. Cristina Maccalli

    Present address: NIBIT-Italian Network for Bio-therapy of Tumors, c/o Medical Oncology and Immunotherapy, Azienda Ospedaliera Universitaria Senese, V.le Bracci, 16, 53100, Siena, Italy

Authors and Affiliations

  1. Unit of Immuno-biotherapy of Melanoma and Solid Tumors, San Raffaele Foundation Centre, Milan, Italy

    Cristina Maccalli

  2. Regina Elena National Cancer Institute, Rome, Italy

    Ruggero De Maria

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  1. Cristina Maccalli
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  2. Ruggero De Maria
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Correspondence to Cristina Maccalli.

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Maccalli, C., De Maria, R. Cancer stem cells: perspectives for therapeutic targeting. Cancer Immunol Immunother 64, 91–97 (2015). https://doi.org/10.1007/s00262-014-1592-1

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