The development and progression of melanoma have been attributed to independent or combined genetic and epigenetic events.,There has been remarkable progress in understanding melanoma pathogenesis in terms of genetic alterations.,However, recent studies have revealed a complex involvement of epigenetic mechanisms in the regulation of gene expression, including methylation, chromatin modification and remodeling, and the diverse activities of non-coding RNAs.,The roles of gene methylation and miRNAs have been relatively well studied in melanoma, but other studies have shown that changes in chromatin status and in the differential expression of long non-coding RNAs can lead to altered regulation of key genes.,Taken together, they affect the functioning of signaling pathways that influence each other, intersect, and form networks in which local perturbations disturb the activity of the whole system.,Here, we focus on how epigenetic events intertwine with these pathways and contribute to the molecular pathogenesis of melanoma.
The incidence of malignant melanoma is increasing.,The majority of patients are diagnosed in early stages when the disease is highly curable.,However, the more advanced or metastatic cases have always been a challenge for clinicians.,The poor prognosis for patients with melanoma is now changing as numerous of promising approaches have appeared recently.,The discovery of aberrations of pathways responsible for intracellular signal transduction allowed us to introduce agents specifically targeting the mutated cascades.,Numerous clinical studies have been conducted to improve effectiveness of melanoma treatment.,From 2011 until now, the U.S.,FDA has approved seven novel agents, such as BRAF-inhibitors (vemurafenib 2011, dabrafenib 2013), MEK-inhibitors (trametinib 2013), anti-PD1 antibodies (nivolumab 2014, pembrolizumab 2014), anti-CTLA-4 antibody (ipilimumab 2011), or peginterferon-alfa-2b (2011) intended to be used in most advanced cases of melanoma.,Nevertheless, clinicians continue working on new possible methods of treatment as resistance to the novel drugs is a commonly observed problem.,This paper is based on latest data published until the end of January 2015.