Clinical implications of acquired braf inhibitors resistance in melanoma

Understanding the role of mitogen-activated protein kinase (MAPK) pathway-activating mutations in the development and progression of melanoma and their possible use as therapeutic targets has substantially changed the management of this neoplasm, which, until a few years ago, was burdened by severe mortality. However, the presence of numerous intrinsic and extrinsic mechanisms of resistance to BRAF inhibitors compromises the treatment responses\u2019 effectiveness and durability. The strategy of overcoming these resistances by combination therapy has proved successful, with the additional benefit of reducing side effects derived from paradoxical activation of the MAPK pathway. Furthermore, the use of other highly specific inhibitors, intermittent dosing schedules and the association of combination therapy with immune checkpoint inhibitors are promising new therapeutic strategies. However, numerous issues related to dose, tolerability and administration sequence still need to be clarified, as is to be expected from currently ongoing trials. In this review, we describe the clinical results of using BRAF inhibitors in advanced melanoma, with a keen interest in strategies aimed at overcoming resistance

Nicotinamide and calcipotriol counteract UVB-induced photoaging on primary human dermal fibroblasts

Background: Photoaging is mainly caused by ultraviolet radiations inasmuch they can damage the DNA, trigger ROS production, and activate p53/p21 pathway, which cause cell cycle arrest and senescence. The accumulationof senescent cells within the dermis contributes to tissue deregulation and skin carcinogenesis. However, the use of photoprotector molecules could reduce UV-induced damages and prevent photoaging. Therefore, the aim of this study is to evaluate whether the active forms of vitamin B3 (nicotinamide) and the analog of vitamin D3 (calcipotriol) might protect primary human dermal fibroblasts (HDFs) from UVB-induced photoaging. Methods: HDFs were isolated from a healthy adult donor and stimulated with nicotinamide (25 μM) and calcipotriol (100 nM) for 24h before UVB exposure, and then, cultured for further 24h on vitamin-supplemented media. Then, cell viability, ROS production, DNA damages, senescence markers, protein and gene expression were evaluated. Results: HDFs treated with nicotinamide and calcipotriol showed better proliferation properties and lower DNA damages due to a reduced UVB-induced ROS production. Consequently, p53/p21 pathway was less active which enhanced cell cycle progression and reduced senescence and cell death. Conclusions: Overall, our results suggest that nicotinamide and calcipotriol can counteract UVB-induced effects responsible for the onset of skin photoaging

Efficacy of topical imiquimod 3.75% in the treatment of actinic keratosis of the scalp in immunosuppressed patients: our case series

AbstractBackground: Actinic keratoses (AK) represent common cutaneous lesions, appearing in 'Field cancerization areas' and potentially evolving toward invasive neoplasm. Immunosuppressed patients ..

Non-Melanoma Skin Cancer: news from microbiota research

Recently, research has been deeply focusing on the role of the microbiota in numerous diseases, either affecting the skin or other organs. What it is well established is that its dysregulation promotes several cutaneous disorders (i.e. psoriasis and atopic dermatitis). To date, little is known about its composition, mediators and role in the genesis, progression and response to therapy of Non-Melanoma Skin Cancer (NMSC). Starting from a bibliographic study, we classified the selected articles into four sections: i) normal skin microbiota; ii) in vitro study models; iii) microbiota and NMSC and iv) probiotics, antibiotics and NMSC. What has emerged is how skin microflora changes, mainly represented by increases of Staphylococcus aureus, Streptococcus pyogenes and Pseudomonas aeruginosa strains, modifications in the mutual quantity of \u3b2-Human papillomavirus genotypes, of Epstein Barr Virus and Malassezia or candidiasis, may contribute to the induction of a state of chronic self-maintaining inflammation, leading to cancer. In this context, the role of S. aureus and that of specific antimicrobial peptides look to be prominent. Moreover, although antibiotics may contribute to carcinogenesis, due to their ability to influence the microbiota balance, specific probiotics, such as Lacticaseibacillus rhamnosus GG, Lactobacillus johnsonii NCC 533 and Bifidobacteria spp., may be protective

Tetracyclines in COVID-19 patients quarantined at home: Literature evidence supporting real-world data from a multicenter observational study targeting inflammatory and infectious dermatoses

Tetracyclines (TetraC) are widely used in dermatology for both inflammatory and infectious dermatoses; recently both in vivo and in vitro studies started to suggest also a potential antiviral effect. During COVID-19 outbreak, several dermatological patients contracted SARS-CoV-2 experiencing only mild symptoms, but no protocol were approved. A multicenter prospective observational study that enrolled COVID-19 patients visited with teledermatology and undergoing TetraC was performed. About 38 adult outpatients (M/F: 20/18, age 42.6 years [21-67]) were enrolled. During the TetraC treatment, symptoms resolved in all patients within 10 days. Remarkably, ageusia and anosmia disappeared in the first week of TetraC treatment. TetraC seem a promising drug to treat COVID-19 outpatients with mild symptoms