The SafeTy Events in VIsmodEgib study (STEVIE, ClinicalTrials.gov, NCT01367665), assessed safety and efficacy of vismodegib-a first-in-class Hedgehog pathway inhibitor demonstrating clinical benefit in advanced basal cell carcinoma (BCC)-in a patient population representative of clinical practice. Primary analysis data are presented. Patients with locally advanced or metastatic BCC received oral vismodegib 150 mg/d until progressive disease, unacceptable toxicity, or withdrawal. Primary objective was safety. Efficacy variables were assessed as secondary end-points. Evaluable adult patients (N = 1215, 1119 locally advanced; 96 metastatic BCC) from 36 countries were treated; 147 patients (12%) remained on study at time of reporting. Median (range) treatment duration was 8.6 (0-44) months. Most patients (98%) had ≥1 treatment-emergent adverse event (TEAE). The incidence of the most common TEAEs was consistent with reports in previous analyses. No association between creatine phosphokinase (CPK) abnormalities and muscle spasm was observed. Serious TEAEs occurred in 289 patients (23.8%). Exposure ≥12 months did not lead to increased incidence or severity of new TEAEs. The majority of the most common TEAEs ongoing at time of treatment discontinuation resolved by 12 months afterwards, regardless of Gorlin syndrome status. Response rates (investigator-assessed) in patients with histologically confirmed measurable baseline disease were 68.5% (95% confidence interval (CI) 65.7-71.3) in patients with locally advanced BCC and 36.9% (95% CI 26.6-48.1) in patients with metastatic BCC. The primary analysis of STEVIE demonstrates that vismodegib is tolerable in typical patients in clinical practice; safety profile is consistent with that in previous reports. Long-term exposure was not associated with worsening severity/frequency of TEAEs. Investigator-assessed response rates showed high rate of tumour control. CLINICALTRIALS.GOV: NCT01367665.

Curcumin is a compound isolated from turmeric, a plant known for its medicinal use. Recently, there is a growing interest in the medical community in identifying novel, low-cost, safe molecules that may be used in the treatment of inflammatory and neoplastic diseases. An increasing amount of evidence suggests that curcumin may represent an effective agent in the treatment of several skin conditions. We examined the most relevant in vitro and in vivo studies published to date regarding the use of curcumin in inflammatory, neoplastic, and infectious skin diseases, providing information on its bioavailability and safety profile. Moreover, we performed a computational analysis about curcumin’s interaction towards the major enzymatic targets identified in the literature. Our results suggest that curcumin may represent a low-cost, well-tolerated, effective agent in the treatment of skin diseases. However, bypass of limitations of its in vivo use (low oral bioavailability, metabolism) is essential in order to conduct larger clinical trials that could confirm these observations. The possible use of curcumin in combination with traditional drugs and the formulations of novel delivery systems represent a very promising field for future applicative research.

Basal cell carcinoma (BCC) is the most common type of carcinoma worldwide. BCC development is the result of a complex interaction between environmental, phenotypic and genetic factors. However, despite the progress in the field, BCC biology and mechanisms of resistance against systemic treatments have been poorly investigated. The aim of the present review is to provide a revision of BCC histological and molecular features, including microRNA (miRNA) dysregulation, with a specific focus on the molecular basis of BCC systemic therapies. Papers from the last ten years regarding BCC genetic and phenotypic alterations, as well as the mechanism of resistance against hedgehog pathway inhibitors vismodegib and sonidegib were included. The involvement of miRNAs in BCC resistance to systemic therapies is emerging as a new field of knowledge.

Alopecia areata (AA) is an organ-specific autoimmune disorder that targets anagen phase hair follicles. The course is unpredictable and current available treatments have variable efficacy. Nowadays, there is relatively little evidence on treatment of AA from well-designed clinical trials. Moreover, none of the treatments or devices commonly used to treat AA are specifically approved by the Food and Drug Administration. The Italian Study Group for Cutaneous Annexial Disease of the Italian Society of dermatology proposes these Italian guidelines for diagnosis and treatment of Alopecia Areata deeming useful for the daily management of the disease. This article summarizes evidence-based treatment associated with expert-based recommendations.

Mitochondria have been considered for long time as important determinants of cell aging because of their role in the production of reactive oxygen species. In this study we investigated the impact of mitochondrial metabolism and biology as determinants of successful aging in primary cultures of fibroblasts isolated from the skin of long living individuals (LLI) (about 100 years old) compared with those from young (about 27 years old) and old (about 75 years old) subjects. We observed that fibroblasts from LLI displayed significantly lower complex I-driven ATP synthesis and higher production of H2O2 in comparison with old subjects. Despite these changes, bioenergetics of these cells appeared to operate normally. This lack of functional consequences was likely due to a compensatory phenomenon at the level of mitochondria, which displayed a maintained supercomplexes organization and an increased mass. This appears to be due to a decreased mitophagy, induced by hyperfused, elongated mitochondria. The overall data indicate that longevity is characterized by a preserved bioenergetic function likely attained by a successful mitochondria remodeling that can compensate for functional defects through an increase in mass, i.e. a sort of mitochondrial "hypertrophy".