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Cancer Stem Cell Challenges in Melanoma Characterization and Treatment

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Cancer Stem Cell Resistance to Targeted Therapy

Part of the book series: Resistance to Targeted Anti-Cancer Therapeutics ((RTACT,volume 19))

Abstract

Melanoma is the most aggressive and lethal form of skin cancer. Many challenges remain despite great progress achieved with recently developed targeted therapies. Melanoma genetic and functional heterogeneity is the major cause of therapy failure, with different subpopulations that can be spared by treatments and which then support tumor regrowth. Many studies have suggested different approaches to isolate and characterize cancer stem cells (CSCs) from melanoma, also known as melanoma-initiating cells (MICs). MICs isolated by different groups can have different phenotypes, and MICs can also show plasticity, switching between MIC and more mature melanoma cell features, further underlying the complexity of this cancer. This chapter describes our current definition of MICs and their identification, with particular attention to their relevance in the therapy resistance. Moreover, we will discuss some of the controversial issues in the field and the possible therapeutic approaches to successfully target melanoma CSCs.

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Abbreviations

ABCB1:

ATP-binding cassette subfamily B member 1

ABCB5:

ATP-binding cassette subfamily B member 5

ABCG2:

ATP-binding cassette subfamily G member 2

ALDH1:

Aldehyde dehydrogenase 1

BRAF:

V-raf murine sarcoma viral oncogene homolog B1

BRAFi:

V-raf murine sarcoma viral oncogene homolog B1 inhibitor

BRAFV600E:

Amino acid substitution at position 600 in BRAF, from a valine (V) to a glutamic acid (E)

CSC:

Cancer stem cell

CD:

Cluster differentiation

CIK:

Cytokine-induced killer

CTLA-4:

Cytotoxic T-lymphocyte antigen-4

CXCL16:

C-X-C motif chemokine ligand 16

CXCR4:

Stromal cell-derived factor-1

CXCR6:

C-X-C motif chemokine receptor 6

EMT:

Epithelial-mesenchymal transition

FDA:

Food and drug administration

JARID1B:

Histone demethylase Jumonji/Arid1b

KIT:

C-Kit tyrosine kinase receptor

IL-6:

Interleukin 6

IL-8:

Interleukin 8

IL-10:

Interleukin 10

MDR1:

Multidrug-resistance gene product 1

MDSC:

Myeloid-derived suppressor cells

MEK:

Mitogen-activated protein kinase kinase

MHC:

Major histocompatibility complex

MIC:

Melanoma-initiating cell

MITF:

Microphthalmia-associated transcription factor

NF-κB:

Nuclear factor kappa b

NGFR:

Nerve growth factor receptor

Notch:

Translocation-associated Notch protein

PD-1:

Programmed cell death-1

RGP:

Radial growth phase

SP:

Side population

TME:

Tumor microenvironment

Treg:

T regulatory cell

UV:

Ultraviolet

VEGFR1:

Vascular endothelial growth factor receptor 1

VGP:

Vertical growth phase

WNT:

Wingless-type mmtv integration site family

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Acknowledgments

This work was supported by AIRC (Associazione Italiana Ricerca sul Cancro) (IG grant: CC IG-10615). The authors are grateful to Dr. Valeria Beretta and Dr. Francesca Rini (Unit of Immunotherapy of Human Tumors, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy) for their active contribution in our melanoma stem cell studies.

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The authors declare no potential conflicts of interest.

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Authors and Affiliations

  1. Unit of Immunotherapy of Human Tumors, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

    Alessandra Tuccitto & Chiara Castelli

  2. Centre for Tumour Biology, Barts Cancer Institute, Charterhouse Square, London, UK

    Malcolm Ronald Alison

  3. The Wistar Institute, Philadelphia, PA, USA

    Michela Perego

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  1. Alessandra Tuccitto
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  2. Chiara Castelli
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  3. Malcolm Ronald Alison
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  4. Michela Perego
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Correspondence to Chiara Castelli or Michela Perego .

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Editors and Affiliations

  1. Research Department, Sidra Medicine, Doha, Qatar

    Cristina Maccalli

  2. Department of DIBIMIS, University of Palermo, Laboratory of Cellular and Molecular Pathophysiology, Palermo, Italy

    Matilde Todaro

  3. Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Soldano Ferrone

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Tuccitto, A., Castelli, C., Alison, M.R., Perego, M. (2019). Cancer Stem Cell Challenges in Melanoma Characterization and Treatment. In: Maccalli, C., Todaro, M., Ferrone, S. (eds) Cancer Stem Cell Resistance to Targeted Therapy. Resistance to Targeted Anti-Cancer Therapeutics, vol 19. Springer, Cham. https://doi.org/10.1007/978-3-030-16624-3_5

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