Neural crest stem cells in melanoma development.
OBJECTIVE
Metastatic melanoma is the most aggressive skin cancer and despite tremendous efforts and considerable progress in clinical treatment of melanoma patients within recent years, it remains a deadly disease. Current treatments affect melanoma cells indiscriminately, while accumulating evidence suggests that melanoma might be a disease of stem cells. This review aims to summarize the important accomplishments in the field and to emphasize the common molecular and cellular mechanisms regulating self-renewal of neural crest stem cells (NCSCs) and melanoma cells.


RESULTS
A growing number of publications highlight the existence of phenotypic and functional similarities between embryonic NCSCs and melanoma cells. These studies provide compelling evidence that the propagation of melanoma cells critically depends on genes instrumental in neural crest development. The example of Sox10 and Rac1 genes provides detailed illustration of how interfering with these important genes for neural crest development can prevent melanoma formation.


CONCLUSIONS
The development of new therapies, targeting RAF-MEK-ERK pathway, provided major improvements in outcomes for patients with metastatic melanoma; however, acquired resistance followed by tumor recurrence represents a major clinical challenge. The striking parallels between embryonic NCSCs (eNCSCs) and melanoma cells might lead to the development of new targeted therapeutics selectively eliminating cell populations accountable for tumor initiation, progression and relapse.
Cell and Developmental Biology, Institute of Anatomy, University of Zurich, Zurich, Switzerland.
Olga
O
Shakhova
D000970:Antineoplastic Agents / Q000627:therapeutic use; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D053263:Gene Regulatory Networks / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008545:Melanoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D009432:Neural Crest / Q000378:metabolism*; D058953:Neural Stem Cells / Q000378:metabolism*; D055757:SOXE Transcription Factors / Q000235:genetics; D012878:Skin Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D020830:rac1 GTP-Binding Protein / Q000235:genetics
D000970:Antineoplastic Agents; C107953:RAC1 protein, human; C527923:SOX10 protein, human; D055757:SOXE Transcription Factors; D020830:rac1 GTP-Binding Protein