Current Controversies and Challenges on BRAF V600K-Mutant Cutaneous Melanoma

About 50% of melanomas harbour a BRAF mutation. Of these 50%, 10% have a V600K mutation. Although it is the second most common driver mutation after V600E, no specific studies have been conducted to identify a clinical and therapeutic gold standard for this patient subgroup. We analysed articles, including registrative clinical trials, to identify common clinical and biological traits of the V600K melanoma population, including different adopted therapeutic strategies. Melanoma V600K seems to be more frequent in Caucasian, male and elderly populations with a history of chronic sun damage and exposure. Prognosis is poor and no specific prognostic factor has been identified. Recent findings have underlined how melanoma V600K seems to be less dependent on the ERK/MAPK pathway, with a higher expression of PI3KB and a strong inhibition of multiple antiapoptotic pathways. Both target therapy with BRAF inhibitors + MEK inhibitors and immunotherapy with anti-checkpoint blockades are effective in melanoma V600K, although no sufficient evidence can currently support a formal recommendation for first line treatment choice in IIIC unresectable/IV stage patients. Still, melanoma V600K represents an unmet medical need and a marker of poor prognosis for cutaneous melanoma

Updates on Potential Therapeutic Approaches for Vitiligo: Janus Kinase Inhibitors and Biologics

Vitiligo, the most prevalent skin depigmenting disease, is characterized by the selective loss of melanocytes, impacting patients’ quality of life significantly. This autoimmune disorder progresses through a complex interplay of genetic and non-genetic factors, posing challenges in comprehending its pathogenesis and devising effective treatment strategies for achieving remission. Existing conventional therapeutic approaches, such as topical and oral corticosteroids, calcineurin inhibitors, and phototherapy, lack specificity, offer modest efficacy, and may entail potential adverse effects. Consequently, there is a pressing need for a more nuanced understanding of vitiligo’s pathogenesis to pave the way for targeted therapeutic innovations. This review aims to provide a comprehensive overview of recent developments and findings concerning Januse Kinase (JAK) inhibitors and biologics tested in vitiligo patients. JAK inhibitors have exhibited promising results, showcasing both efficacy and tolerability. In contrast, the outcomes of biologics treatment have been more varied. However, to establish a clearer understanding of which specific pathways to target for a more effective approach to vitiligo, additional in vitro studies and extensive clinical research involving a larger population are imperative