Next Generation Sequencing (NGS) and Cancer: New Steps Towards Personalized Medicine

Erika Bandini^1*Clévia Rosset^2,3

• ¹Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy., Meldola, Italy
• ²Laboratory of Genomic Medicine, Experimental Research Service, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil, Porto Alegre, Brazil
• ³Post-Graduation Program of Medical Sciences, Federal University of Rio Grande do Sul, Porto Alegre, Brazil., Porto Alegre, Brazil

Next Generation Sequencing (NGS) and Cancer: New Steps Towards Personalized MedicineIn the era of precision oncology, the scenario of cancer diagnostics, prognostics, and therapeutics has been revolutionized by the advent of next-generation sequencing (NGS). The ability to investigate cancer genomes and transcriptomes at remarkable depth has enabled the identification of novel mutations, fusion events, gene expression profiles, and non-coding RNA (ncRNA) signatures that contribute to tumorigenesis and therapeutic resistance. This Research Topic, Next Generation Sequencing (NGS) and Cancer: New Steps Towards Personalized Medicine, has been conceived to explore how NGS technologies continue to drive forward the era of personalized oncology. This collection, including original research and case reports, reflects the diversity and translational potential of NGS across tumor types and clinical contexts. The contributions cover key areas of precision oncology, ranging from biomarker discovery and drug sensitivity profiling to clinical case studies, that highlight the practical utility of NGS in guiding targeted therapies. Several studies emphasize the growing role of integrative bioinformatics and machine learning in finding out actionable insights from complex datasets. For example, Cui et al. applied topological data analysis and deep learning to uncover molecular drivers and predict therapeutic targets in melanoma, exploiting immune gene regulatory networks constructed from NGS data. Their computational approach exemplifies how artificial intelligence can bridge network-based analysis with precision oncology. Prognostic stratification is another critical application of NGS. Xu et al. performed a comprehensive analysis of programmed cell death (PCD) modalities in cholangiocarcinoma, integrating immune microenvironment features and drug sensitivity profiles. Their multidimensional approach stratified patients into prognostic subgroups and highlighted pathways that could inform personalized treatment strategies for this rare and aggressive cancer. Collectively, the articles in this Research Topic exemplify how NGS is reshaping oncology across research and clinical practice, from molecular discovery to clinical decision-making. Several contributions explore the identification of novel fusion genes, regulatory RNAs, and resistance mechanisms, while others focus on integrating multi-omic data, refining prognostic models, or demonstrating NGS-guided therapeutic interventions. These studies highlight the critical need to integrate high-throughput sequencing data into clinical workflows, in order to optimize treatment strategies and improve patient outcomes. They also reveal the ongoing need for reliable bioinformatics pipelines, functional validation, and close interdisciplinary collaboration among researchers, oncologists, pathologists, and bioinformaticians. As NGS technologies continue to evolve, becoming faster, more affordable, and more accessible, they are increasingly positioned to serve as core components of routine oncology care. To fully realize their potential, this technological progress must be accompanied by collaborative efforts to standardize data interpretation, address ethical considerations around genomic information, and ensure equitable access to testing across all patient populations. This Research Topic reflects the rapid advancement in the integration of genomics into clinical practice, offering novel insights into the molecular drivers of cancer and illustrating how precision oncology is already transforming patient care.