Epigenetic alterations have emerged as essential contributors in the pathogenesis of various human diseases, including cutaneous melanoma (CM). Unlike genetic changes, epigenetic modifications are highly dynamic and reversible and thus easy to regulate. Here, we present a comprehensive review of the latest research findings on the role of genetic and epigenetic alterations in CM initiation and development. We believe that a better understanding of how aberrant DNA methylation and histone modifications, along with other molecular processes, affect the genesis and clinical behavior of CM can provide the clinical management of this disease a wide range of diagnostic and prognostic biomarkers, as well as potential therapeutic targets that can be used to prevent or abrogate drug resistance. We will also approach the modalities by which these epigenetic alterations can be used to customize the therapeutic algorithms in CM, the current status of epi-therapies, and the preliminary results of epigenetic and traditional combinatorial pharmacological approaches in this fatal disease.
Carbapenem-resistant Enterobacterales (CRE) are included in the list of the most threatening antibiotic resistance microorganisms, being responsible for often insurmountable therapeutic issues, especially in hospitalized patients and immunocompromised individuals and patients in intensive care units. The enzymatic resistance to carbapenems is encoded by different β-lactamases belonging to A, B or D Ambler class. Besides compromising the activity of last-resort antibiotics, CRE have spread from the clinical to the environmental sectors, in all geographic regions. The purpose of this review is to present present and future perspectives on CRE-associated infections treatment.
Skin cancer, which includes the most frequent malignant non-melanoma carcinomas (basal cell carcinoma, BCC, and squamous cell carcinoma, SCC), along with the difficult to treat cutaneous melanoma (CM), pose important worldwide issues for the health care system. Despite the improved anti-cancer armamentarium and the latest scientific achievements, many skin cancer patients fail to respond to therapies, due to the remarkable heterogeneity of cutaneous tumors, calling for even more sophisticated biomarker discovery and patient monitoring approaches. Droplet digital polymerase chain reaction (ddPCR), a robust method for detecting and quantifying low-abundance nucleic acids, has recently emerged as a powerful technology for skin cancer analysis in tissue and liquid biopsies (LBs). The ddPCR method, being capable of analyzing various biological samples, has proved to be efficient in studying variations in gene sequences, including copy number variations (CNVs) and point mutations, DNA methylation, circulatory miRNome, and transcriptome dynamics. Moreover, ddPCR can be designed as a dynamic platform for individualized cancer detection and monitoring therapy efficacy. Here, we present the latest scientific studies applying ddPCR in dermato-oncology, highlighting the potential of this technology for skin cancer biomarker discovery and validation in the context of personalized medicine. The benefits and challenges associated with ddPCR implementation in the clinical setting, mainly when analyzing LBs, are also discussed.
Since the discovery of penicillin by Alexander Fleming in 1929 as a therapeutic agent against staphylococci, β-lactam antibiotics (BLAs) remained the most successful antibiotic classes against the majority of bacterial strains, reaching a percentage of 65% of all medical prescriptions. Unfortunately, the emergence and diversification of β-lactamases pose indefinite health issues, limiting the clinical effectiveness of all current BLAs. One solution is to develop β-lactamase inhibitors (BLIs) capable of restoring the activity of β-lactam drugs. In this review, we will briefly present the older and new BLAs classes, their mechanisms of action, and an update of the BLIs capable of restoring the activity of β-lactam drugs against ESKAPE (Enterococcus spp., Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) pathogens. Subsequently, we will discuss several promising alternative approaches such as bacteriophages, antimicrobial peptides, nanoparticles, CRISPR (clustered regularly interspaced short palindromic repeats) cas technology, or vaccination developed to limit antimicrobial resistance in this endless fight against Gram-negative pathogens.
Whether acquired or de novo, drug resistance remains a significant hurdle in achieving therapeutic success in breast cancer (BC). Thus, there is an urge to find reliable biomarkers that will help in predicting the therapeutic response. Stable and easily accessible molecules such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are regarded as valuable prognostic biomarkers and therapeutic targets since they act as crucial regulators of the various mechanisms involved in BC drug resistance. Here, we reviewed the current literature on ncRNAs as mediators of resistance to systemic therapies in BC. Interestingly, upon integrating data results from individual studies, we concluded that miR-221, miR-222, miR-451, Urothelial Carcinoma Associated 1 (UCA1), and Growth arrest-specific 5 (GAS5) are strong candidates as prognostic biomarkers and therapeutic targets since they are regulating multiple drug resistance phenotypes in BC. However, further research around their clinical implications is needed to validate and integrate them into therapeutic applications. Therefore, we believe that our review may provide relevant evidence for the selection of novel therapeutic targets and prognostic biomarkers for BC and will serve as a foundation for future translational research in the field.
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