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Review
. 2022 Apr 23;14(9):2104.
doi: 10.3390/cancers14092104.

The Genetic Basis of Dormancy and Awakening in Cutaneous Metastatic Melanoma

Agata Janowska  1 , Michela Iannone  1 , Cristian Fidanzi  1 , Marco Romanelli  1 , Luca Filippi  2 , Marzia Del Re  3 , Manuella Martins  1 , Valentina Dini  1
Affiliations
Review

The Genetic Basis of Dormancy and Awakening in Cutaneous Metastatic Melanoma

Agata Janowska et al. Cancers (Basel). .

Abstract

Immune dysregulation, in combination with genetic and epigenetic alterations, induces an excessive proliferation of uncontrolled melanoma cells followed by dissemination of the tumor cells to distant sites, invading organs and creating metastasis. Although immunotherapy, checkpoint inhibitors and molecular targeted therapies have been developed as treatment options for advanced melanoma, there are specific mechanisms by which cancer cells can escape treatment. One of the main factors associated with reduced response to therapy is the ability of residual tumor cells to persist in a dormant state, without proliferation. This comprehensive review aimed at understanding the genetic basis of dormancy/awakening phenomenon in metastatic melanoma will help identify the possible therapeutical strategies that might eliminate melanoma circulating tumor cells (CTCs) or keep them in the dormant state forever, thereby repressing tumor relapse and metastatic spread.

Keywords: clinical latency; dormant state; malignant melanoma; metastatic melanoma.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The main factors contributing to the process of melanoma dormancy: cellular dormancy, angiogenic dormancy and immune-mediated dormancy.
See this image and copyright information in PMC

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References

    1. Carr S., Smith C., Wernberg J. Epidemiology and risk factors of melanoma. Surg. Clin. N. Am. 2020;100:1–12. doi: 10.1016/j.suc.2019.09.005. - DOI - PubMed
    1. Chopra A., Sharma R., Rao U.N.M. Pathology of Melanoma. Surg. Clin. N. Am. 2020;100:43–59. doi: 10.1016/j.suc.2019.09.004. - DOI - PubMed
    1. Berk-Krauss J., Stein J.A., Weber J., Polsky D., Geller A.C. New systematic therapies and trends in cutaneous melanoma deaths among US Whites, 1986–2016. Am. J. Public Health. 2020;110:731–733. doi: 10.2105/AJPH.2020.305567. - DOI - PMC - PubMed
    1. Merlino G., Herlyn M., Fisher D.E., Bastian B.C., Flaherty K.T., Davies M.A., Wargo J.A., Curiel Lewandrowski C., Weber M.J., Leachman S.A., et al. The state of melanoma: Challenges and opportunities. Pigment Cell Melanoma Res. 2016;29:404–416. doi: 10.1111/pcmr.12475. - DOI - PMC - PubMed
    1. Rebecca V.W., Sondak V.K., Smalley K.S.M. A brief history of melanoma: From mummies to mutations. Melanoma Res. 2013;22:114–122. doi: 10.1097/CMR.0b013e328351fa4d. - DOI - PMC - PubMed

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