ABSTRACT
Advances in melanoma research have unveiled critical insights into its genetic and molecular landscape, leading to significant therapeutic innovations. This review explores the intricate interplay between genetic alterations, such as mutations in BRAF, NRAS, and KIT, and melanoma pathogenesis. The MAPK and PI3K/Akt/mTOR signaling pathways are highlighted for their roles in tumor growth and resistance mechanisms. Additionally, this review delves into the impact of epigenetic modifications, including DNA methylation and histone changes, on melanoma progression. The tumor microenvironment, characterized by immune cells, stromal cells, and soluble factors, plays a pivotal role in modulating tumor behavior and treatment responses. Emerging technologies like single-cell sequencing, CRISPR-Cas9, and AI-driven diagnostics are transforming melanoma research, offering precise and personalized approaches to treatment. Immunotherapy, particularly immune checkpoint inhibitors and personalized mRNA vaccines, has revolutionized melanoma therapy by enhancing the body's immune response. Despite these advances, resistance mechanisms remain a challenge, underscoring the need for combined therapies and ongoing research to achieve durable therapeutic responses. This comprehensive overview aims to highlight the current state of melanoma research and the transformative impacts of these advancements on clinical practice.
ABSTRACT
Genomics has significantly revolutionized pathogen surveillance, particularly in epidemiological studies, the detection of drug-resistant strains, and disease control. Despite its potential, the representation of Latin American countries in the genomic catalogues of Mycobacterium tuberculosis (Mtb), the bacteria responsible for Tuberculosis (TB), remains limited. In this study, we present a whole genome sequencing (WGS)-based analysis of 85 Mtb clinical strains from 17 Mexican states, providing insights into local adaptations and drug resistance signatures in the region. Our results reveal that the Euro-American lineage (L4) accounts for 94% of our dataset, showing 4.1.2.1 (Haarlem, n = 32), and 4.1.1.3 (X-type, n = 34) sublineages as the most prevalent. We report the presence of the 4.1.1.3 sublineage, which is endemic to Mexico, in six additional locations beyond previous reports. Phenotypic drug resistance tests showed that 34 out of 85 Mtb samples were resistant, exhibiting a variety of resistance profiles to the first-line antibiotics tested. We observed high levels of discrepancy between phenotype and genotype associated with drug resistance in our dataset, including pyrazinamide-monoresistant Mtb strains lacking canonical variants of drug resistance. Expanding the Latin American Mtb genome databases will enhance our understanding of TB epidemiology and potentially provide new avenues for controlling the disease in the region.