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’ 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.     

Determination of Pesticides in Wheat Flour Using Microextraction on Packed Sorbent Coupled to Ultra-High Performance Liquid Chromatography and Tandem Mass Spectrometry

An ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC–MS/MS) method for multiclass analysis of pesticide and fungicide residues in wheat flour based is presented. An efficient and rapid cleanup based on microextraction by packed sorbent (MEPS) has been developed in order to have a good enrichment factor together with a low matrix effect. The target analytes were 25 pesticides widely used in wheat, with different physico-chemical characteristics and different mechanism of action: acetylcholinesterase inhibitors such as organophosphorus, carbamates, neonicotinoids, and inhibitors of ergosterol such as imidazoles and triazoles. MEPS was shown to be successful with reduction of the amount of solvent required and possibility of automation of the cleanup procedure. The whole method was then validated according to the SANCO/12571/2013 guidelines, proving its suitability as confirmation method for the selected analytes.     

Prostate Cancer Radiogenomics—From Imaging to Molecular Characterization

Radiomics and genomics represent two of the most promising fields of cancer research, designed to improve the risk stratification and disease management of patients with prostate cancer (PCa). Radiomics involves a conversion of imaging derivate quantitative features using manual or automated algorithms, enhancing existing data through mathematical analysis. This could increase the clinical value in PCa management. To extract features from imaging methods such as magnetic resonance imaging (MRI), the empiric nature of the analysis using machine learning and artificial intelligence could help make the best clinical decisions. Genomics information can be explained or decoded by radiomics. The development of methodologies can create more-efficient predictive models and can better characterize the molecular features of PCa. Additionally, the identification of new imaging biomarkers can overcome the known heterogeneity of PCa, by non-invasive radiological assessment of the whole specific organ. In the future, the validation of recent findings, in large, randomized cohorts of PCa patients, can establish the role of radiogenomics. Briefly, we aimed to review the current literature of highly quantitative and qualitative results from well-designed studies for the diagnoses, treatment, and follow-up of prostate cancer, based on radiomics, genomics and radiogenomics research.