Integrative Cancer Genomics and Multi-Omics Approaches to Decode Structural Variation, Tumor Heterogeneity, and Therapeutic Vulnerabilities

Cancer is driven by complex genomic and epigenomic alterations that influence tumor initiation, progression, treatment response, and resistance. While single-gene mutations have been extensively studied, growing evidence highlights the importance of broader genome architecture, including structural variants, copy-number alterations, gene fusions, chromothripsis, and other large-scale rearrangements. These events can disrupt tumor suppressor genes, activate oncogenes, alter regulatory elements, and reshape transcriptional programs. Recent advances in next-generation sequencing, long-read sequencing, optical genome mapping, single-cell profiling, spatial technologies, and computational multi-omics integration now provide unprecedented opportunities to link genomic alterations with functional consequences. However, translating these complex datasets into clinically meaningful biomarkers and therapeutic strategies remains a major challenge.The goal of this Research Topic is to bring together recent advances that improve our understanding of how genomic alterations shape cancer biology and clinical behavior. A major challenge in cancer genomics is moving beyond cataloging alterations toward identifying which events are functionally important, clinically actionable, and biologically informative. By highlighting studies that integrate genomic, transcriptomic, epigenomic, and computational approaches, this collection aims to provide a comprehensive overview of how multi-omics strategies can refine cancer classification, uncover mechanisms of tumor progression, and reveal new therapeutic opportunities. This Research Topic will also emphasize methodological advances that improve detection, interpretation, and prioritization of complex genomic events, including structural variants and noncoding alterations. Collectively, the articles in this collection will help bridge the gap between cancer genome discovery and translational application.This Research Topic welcomes Original Research, Reviews, Mini-Reviews, Perspectives, Methods, and Brief Research Reports focused on integrative approaches in cancer genetics and oncogenomics. We particularly encourage contributions addressing:• Structural variation, copy-number alteration, and gene fusion landscapes in cancer • Integration of DNA, RNA, epigenomic, proteomic, single-cell, and spatial datasets • Functional interpretation of cancer-associated genomic rearrangements• Computational frameworks for multi-omics biomarker discovery• Tumor heterogeneity, clonal evolution, and therapy resistance• Genomic predictors of treatment response and therapeutic vulnerability• Emerging technologies such as long-read sequencing and optical genome mapping driven cancer genomics Topic editors: Rahul Kumar, PRANAY TANWAR Source: https://www.frontiersin.org/research-topics/82911/integrative-cancer-genomics-and-multi-omics-approaches-to-decode-structural-variation-tumor-heterogeneity-and-therapeutic-vulnerabilities