Recent work has expanded our knowledge in somatic genetic events related to melanoma progression. It has become increasingly clear that multiple genetic events are required for melanoma to develop and that melanoma is a vastly heterogeneous disease. Signaling pathways that are essential for tumor progression have been pinpointed due to recent technological developments, which has led to the vigorous pursuit of small molecule kinase inhibitors and the eventual FDA approval of novel MAPK pathway inhibitors for the treatment of advanced melanoma (see Chaps. 7 and 16). As has been implicated in many other malignancies, molecular profiling is further anticipated to reveal prognostic, diagnostic, and predictive tools in the clinical setting of melanoma.Additionally, tumor genetic data have been interconnected with epidemiology of melanoma (see Chap. 3). Two etiological pathways have been postulated to trigger the formation of melanoma. The first pathway involves relatively young individuals with large numbers of nevi and who develop melanomas on locations (e.g., trunk) that are intermittently UV exposed. This pathway is further corroborated by the fact that BRAF mutations, which frequently occur in nevi, are also more common in melanomas of younger patients with larger number of moles. A second pathway, which is probably related to chronic UV exposure, leads to melanomas that develop among older individuals and on chronically sun-exposed sites. Additionally, genetic analyses have uncovered a previously undisclosed hidden molecular structure between subtypes of melanoma. Along translational lines, tumor genetic information has recently shown to be of enormous significance for personalizing therapeutic choice, e.g., Braf inhibitors that selectively target BrafV600E mutated melanomas and Mek inhibitors that target the MAPK pathway in metastatic melanoma; thus tumor genetic information is required prior to treatment. Moreover, molecular studies have also begun to shed light onto mechanisms of resistance that develop in the context of treatment with Braf and/or Mek inhibitors. In this chapter, we have screened current literature for an update of genetics and genomics within the field of melanoma tumor biology.
|Titel på värdpublikation||Melanoma Development|
|Undertitel på värdpublikation||Molecular Biology, Genetics and Clinical Application|
|Redaktörer||A. K. Bosserhoff|
|Förlag||Springer International Publishing|
|Status||Published - 2017|
- Cancer och onkologi