RESUMO
The number of treatment options for melanoma patients has grown in the past few years, leading to considerable improvements in both overall and progression-free survival. Targeted therapies and immune checkpoint inhibitors have opened a new era in the management of melanoma patients. Despite the clinical advances, further research efforts are needed to identify other "druggable" targets and new biomarkers to improve the stratification of melanoma patients who could really benefit from targeted and immunotherapies. To this end, many studies have focused on the role of microRNAs (miRNAs) that are small non-coding RNAs (18-25 nucleotides in length), which post-transcriptionally regulate the expression of their targets. In cancer, they can behave either as oncogenes or oncosuppressive genes and play a central role in many intracellular pathways involved in proliferation and invasion. Given their modulating activity on the transcriptional landscape, their biological role is under investigation to study resistance mechanisms. They are able to mediate the communication between tumor cells and their microenvironment and regulate tumor immunity through direct regulation of the genes involved in immune activation or suppression. To date, a very promising miRNA-based strategy is to use them as prognosis and diagnosis biomarkers both as cell-free miRNAs and extracellular-vesicle miRNAs. However, miRNAs have a complex role since they target different genes in different cellular conditions. Thus, the ultimate aim of studies has been to recapitulate their role in melanoma in biological networks that account for miRNA/gene expression and mutational state. In this review, we will provide an overview of current scientific knowledge regarding the oncogenic or oncosuppressive role of miRNAs in melanoma and their use as biomarkers, with respect to approved therapies for melanoma treatment.
Assuntos
Biomarcadores Tumorais/genética , Carcinogênese/genética , Melanoma/genética , MicroRNAs/genética , Neoplasias Cutâneas/genética , Gerenciamento Clínico , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Melanoma/patologia , Melanoma/terapia , Prognóstico , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapia , Microambiente Tumoral/genética , Melanoma Maligno CutâneoRESUMO
In clinical trials, a sofosbuvir/velpatasvir (SOF/VEL) pangenotypic single-tablet regimen was associated with high sustained virological response (SVR) rates at 12 weeks (SVR12) after the end of treatment, regardless of genotype and fibrosis stage. No real-life data on genotype 3 (GT3) cirrhotic patients with portal hypertension are available. The aim of this study was to assess the effectiveness of SOF/VEL in GT3 cirrhotics with portal hypertension. Patients with GT3 and advanced cirrhosis were treated for 12 weeks with SOF/VEL without ribavirin at five different centers in Italy from June 2017 to August 2018 and their SVR12 was assessed. Of the 227 GT3 cirrhotics evaluated, 205 met the inclusion criteria and 111 had transient elastography results ≥20 KPa. SVR12 was 97.6% (95% CI 94.4-98.9), rates were 99.1% (95% CI 95.7-99.8) in patients with ≥20 KPa and 95.8% (95% CI 89.5-98.3) in those with <20 KPa (p = 0.18). Analyzed by presence of esophageal varices, the SVR12 rates were 98.4% (95% CI 91.4-99.7) and 97.1% (95% CI 92.9-98.9) in patients without and with varices, respectively (p = 1.0). In real life, SOF/VEL GT3 cirrhotic patients with evidence of portal hypertension can achieve SVR12 levels comparable to those of patients without portal hypertension. These SVR12 rates are similar to what is reported in compensated cirrhosis treated within clinical trials.