cAMP-mediated regulation of melanocyte genomic instability: A melanoma-preventive strategy

Nathaniel C. Holcomb, Robert Marlo Bautista, Stuart G. Jarrett, Katharine M. Carter, Madeline Krentz Gober, John A. D'Orazio

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

9 Scopus citations

Abstract

Malignant melanoma of the skin is the leading cause of death from skin cancer and ranks fifth in cancer incidence among all cancers in the United States. While melanoma mortality has remained steady for the past several decades, melanoma incidence has been increasing, particularly among fair-skinned individuals. According to the American Cancer Society, nearly 10,000 people in the United States will die from melanoma this year. Individuals with dark skin complexion are protected damage generated by UV-light due to the high content of UV-blocking melanin pigment in their epidermis as well as better capacity for melanocytes to cope with UV damage. There is now ample evidence that suggests that the melanocortin 1 receptor (MC1R) is a major melanoma risk factor. Inherited loss-of-function mutations in MC1R are common in melanoma-prone persons, correlating with a less melanized skin complexion and poorer recovery from mutagenic photodamage. We and others are interested in the MC1R signaling pathway in melanocytes, its mechanisms of enhancing genomic stability and pharmacologic opportunities to reduce melanoma risk based on those insights. In this chapter, we review melanoma risk factors, the MC1R signaling pathway, and the relationship between MC1R signaling and DNA repair.

Original languageEnglish
Title of host publicationAdvances in Protein Chemistry and Structural Biology
Pages247-295
Number of pages49
DOIs
StatePublished - Jan 1 2019

Publication series

NameAdvances in Protein Chemistry and Structural Biology
Volume115
ISSN (Print)1876-1623

Bibliographical note

Funding Information:
This work was supported by the following NIH grants: R01 CA131075, P30 CA177558, 2T32 CA160003-06A1, and 5T32 CA165990-06. We thank the Melanoma Research Alliance, the Regina Drury Pediatric Research Endowed Chair Fund, the Wendy Will Case Cancer Research Fund, the Markey Cancer Foundation, the Children's Miracle Network, and the Jennifer and David Dickens Melanoma Research Foundation. We thank the Markey Cancer Center's Research Communications Office for assistance with figure preparation. The authors would like to state that there are no conflicts of interest that arose during the preparation of this manuscript.

Funding Information:
This work was supported by the following NIH grants: R01 CA131075, P30 CA177558, 2T32 CA160003-06A1, and 5T32 CA165990-06. We thank the Melanoma Research Alliance, the Regina Drury Pediatric Research Endowed Chair Fund, the Wendy Will Case Cancer Research Fund, the Markey Cancer Foundation, the Children's Miracle Network, and the Jennifer and David Dickens Melanoma Research Foundation. We thank the Markey Cancer Center's Research Communications Office for assistance with figure preparation.

Publisher Copyright:
© 2019 Elsevier Inc.

Keywords

  • ATR
  • MC1R
  • Melanin
  • Melanoma
  • Mutation
  • Nucleotide excision repair
  • Risk
  • UV
  • cAMP

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry

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