Clinical assessment of skin phototypes: watch your words!

Fitzpatrick skin phototype classification is widely used to assess risk factors for skin cancers. This skin type evaluation is easy to use in clinical practice but is not always applied as initially described, nor practiced in a standardised way. This can have implications on the results of relevant dermato-epidemiological studies. To demonstrate, in a large multinational setting, that the phrasing of questions on sun sensitivity can have a strong impact on the perception and reporting of skin phototype, as well as the importance of a standardised procedure for phototype assessment. Using data collected from 48,258 screenees of the Euromelanoma campaign in six European countries from 2009 to 2011, we analysed the impact of change in the question phrasing on phototype classification in each country. Changing the wording of a question to assess the phototype of a person also significantly influenced the classification of phototypes in different countries (p<0.001 for each country). The difference essentially corresponded to a shift towards a less sun-sensitive skin type when a shorter question that did not include skin colour description was used. The only exception was Portugal where phototype was not patient-assessed and classification shifted towards a more sun-sensitive phototype. Results were statistically significant and highly consistent, irrespective of gender. The phrasing of questions on skin type is important and substantially influences reporting. A standardized procedure to classify phototypes should be used in order to obtain comparable data between studies

Tretinoin-based formulations - influence of concentration and vehicles on skin penetration

Tretinoin is used in the management of acne and it is part of a gold standard treatment for photoaging. It has also been reported as an agent for superficial chemical peeling in highly concentrated formulations with few considerations about skin penetration. The aim of this study was to evaluate the influence of drug concentration and vehicles currently used on skin penetration of tretinoin. In vitro permeation tests were carried out using Franz diffusion cells fitted with porcine ear skin and 10% aqueous methanol in the receptor compartment. Formulations studied, cream or hydroalcoholic dispersion, containing 0.25%, 1% and 5% of tretinoin were placed in the donor compartment for six hours. Tretinoin concentration in skin layers was measured by high performance liquid chromatography. The largest amount of tretinoin from both vehicles was detected in stratum corneum with significant differences among the three concentrations. The hydroalcoholic dispersion was the best vehicle. Significant amounts of tretinoin were found even in deep layers of epidermis. The formulation with 0.25% tretinoin showed better results when considered the amount of tretinoin on skin in terms of percentage. Finally, skin penetration of tretinoin was influenced by vehicle and concentration of this drug used in formulation

Lessons from genome-wide studies of melanoma: towards precision medicine

Introduction: Cutaneous melanoma is a malignancy with complex aetiology that could be considered as a result of interplay between phenotypic characteristics, various environmental exposures and genetic variants. Areas covered: Several genes have been found to be robustly associated with risk for melanoma. Emerging approaches such as genome-wide association studies have revealed several such postulated genes but most of the identified loci have weak to moderate risk effects, with Odds Ratios ranging, mostly, between 1.10 and 1.40. Ideally, such discoveries could shift research towards precision or individualized medicine on the prevention front and could lead to better individual risk prediction; however current findings have not highlighted adequate number of disease pathways or variants with large effect sizes and population attributable risk. Expert commentary: The potential impact of larger studies and big data to improve health, prevent and detect melanoma at an earlier stage and personalize interventions could be tremendous in the near future. © 2016 Informa UK Limited, trading as Taylor & Francis Group

New targeted approaches for the treatment and prevention of nonmelanoma skin cancer

Cutaneous squamous cell carcinoma and basal cell carcinomas, commonly termed 'nonmelanoma skin cancer' or 'epithelial skin cancers', are among the most common cancers in white-skinned populations. The most prevalent risk factors that contribute to the pathogenesis of epithelial skin cancers include excessive exposure to UV radiation, pigmentary traits and genetic predisposition. A wide range of different treatment modalities have been used with the aim to eradicate the tumor while maintaining an acceptable cosmetic outcome. Surgical excision, Moh's micrographic surgery, cryosurgery, curettage and electrodesiccation, radiotherapy, photodynamic therapy, as well as topical pharmacological agents (e.g., topical imiquimod, 5-fluorouracil) are currently employed, based on the individual tumor and patient characteristics. New insights into the pathogenesis of basal cell carcinomas and squamous cell carcinoma have led to the development of targeted treatments, such as hedgehog signaling pathway inhibitors, ornithine decarboxylase inhibitors, cyclooxygenase inhibitors and anti-EGF receptor inhibitors that are currently being tested for efficacy and safety in clinical trials. This review provides an up-to-date overview of novel and emerging systemic and topical treatments for epithelial skin cancers and discusses the rationale for their use in the evolving therapeutic landscape of these tumors. © 2011 Expert Reviews Ltd

From basal cell carcinoma morphogenesis to the alopecia induced by hedgehog inhibitors: connecting the dots

The deciphering of the hedgehog (Hh) signalling pathway implicated in the tumorigenesis of basal cell carcinoma (BCC) led to the development of targeted drug therapies, the Hh pathway inhibitors (HPIs) vismodegib and sonidegib. In the skin, physiological Hh signalling is activated in growing hair follicles (HFs), where it is required for proliferation of the epithelium of HFs during morphogenesis and for their postnatal growth. The effects of HPI treatment leading to the regression of BCC and the development of alopecia underpin the central role of the Hh pathway in BCC formation, as well as hair cycling. Given the fact that BCC is a follicular-driven tumour, it is a fine tuning of events that regulate hair cycling that may drive towards the formation of benign follicular hamartomas or malignant BCC neoplasms. Wnt/β-catenin signalling interacts with the Hh signalling during HF morphogenesis, normal hair cycling and BCC development. The aim of this review is to present how key molecular events implicated in Hh pathway crosstalk in the HF are also involved in BCC pathogenesis and result in the alopecia developed by HPI treatment. © 2017 British Association of Dermatologist

Vismodegib for the treatment of basal cell carcinoma: Results and implications of the ERIVANCE BCC trial

The need for effective treatment of patients with locally advanced or metastatic basal cell carcinoma (BCC), in conjunction with major advances in the elucidation of the molecular basis of this tumor has led to the advent of new targeted therapies - namely, hedgehog inhibitors. The rationale for their use in patients with advanced BCC is based on their inhibitory effect on the hedgehog pathway, which is aberrantly activated in BCCs due to mutations of its primary components, PTCH1 and SMO genes. Vismodegib (GDC-0449) is an orally bioavailable hedgehog pathway inhibitor that selectively inhibits SMO. The ERIVANCE BCC study is a Phase II, international, multicenter clinical trial evaluating the efficacy and safety of vismodegib 150 mg once daily in patients with locally advanced or metastatic BCC. Vismodegib has been approved for the treatment of adult patients with metastatic BCC, or with locally advanced BCC that has recurred following surgery or who are not candidates for surgery or radiation therapy. This article will outline the rationale, design and available results from the ERIVANCE BCC study and discuss the clinical implications of vismodegib in the management of patients with BCC. Challenges regarding vismodegib use include the recurrence of BCC after drug discontinuation, the development of acquired resistance, the dramatic efficacy in patients with Gorlin syndrome, and class-related drug toxicity. Ongoing clinical trials aim to explore the role of vismodegib in the neoadjuvant setting prior to surgery, the potential use of alternate dosing regimens in order to limit chronic adverse events, as well as the identification of patients with BCC that are more likely to respond to this targeted therapy based on genotypic and/or phenotypic characteristics. © 2014 Future Medicine Ltd

Advances and trends in dermato-oncology

The 6th Congress of the European Association of Dermato-Oncology, held in Athens, Greece (16-19 June 2010), focused on the most recent advances in the field of melanoma, epithelial skin cancers and other malignant skin tumors. Under the theme 'transforming care through personalized medicine, the scientific program reviewed and discussed the significant changes that are currently taking place in many aspects of skin cancer care, from risk prediction and prevention to the use of targeted treatments. This article highlights the key messages from selected presentations that feature the remarkable progress in our understanding of the pathogenesis of skin malignancies and the rapid 'translation of this knowledge into new effective treatments in clinical practice. © 2010 Expert Reviews Ltd

Pharmacologic treatment options for advanced epithelial skin cancer

Introduction: Epithelial skin cancers (ESCs), namely basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs), are considered common skin malignancies, with rising incidence rates over the past few decades. A subgroup of patients with ESC present with advanced and 'difficult'-to-treat tumours, including locally advanced and metastatic tumours. Currently, there is no widely accepted staging system for locally advanced ESCs, while metastatic BCCs and SCCs share a staging system. Therefore, selecting an appropriate therapeutic regimen for these patients may be difficult.Areas covered: The purpose of this review is to highlight the pharmacologic treatment options for advanced ESCs. These include 'conventional' chemotherapeutic regimens such as 5-fluorouracil, cisplatin, vincristine, bleomycin and doxorubicin and newer, more 'targeted' therapies.Expert opinion: Vismodegib, a Hedgehog (Hh) inhibitor, was recently approved for the treatment of advanced BCC showing a good efficacy rate and a relatively well-tolerated safety profile in clinical studies. In addition, a number of hedgehog inhibitors are now in Phase I and II trials of advanced BCC demonstrating encouraging results. Phase II studies with epithelial growth factor receptor inhibitors, such as cetuximab, gefitinib, panitimumab and erlotinib have been conducted in patients with advanced SCCs, used either as monotherapy or in combination with chemotherapy. However, there is still much knowledge to be gained about the treatment efficacies, optimal treatment durations, mechanisms of drug tolerance, adverse events and the ways in which these therapies influence patient outcomes and quality of life. © 2015 Informa UK, Ltd