Mechanisms Promoting Mutation Generation in Cancer

Somatic mutations drive cancer initiation, progression, and therapeutic resistance. Advances in whole genome and transcriptome sequencing have revealed the extensive genomic heterogeneity present even within individual tumors, highlighting that mutation accumulation is a dynamic, ongoing process throughout tumor evolution. Despite major progress in cataloguing cancer associated mutations, the biological mechanisms that generate these alterations remain only partially understood. Increasing evidence suggests that tumor specific changes in cellular metabolism, mitochondrial function, and redox balance, can directly influence DNA stability by shaping the intracellular environment in which mutations arise. Understanding the molecular drivers that initiate and sustain high mutation rates will provide essential insights into explaining tumor evolution, therapeutic resistance, and metastatic progression.The goal of this Research Topic is to explore the mechanistic origins of elevated mutation rates in cancer, outside the classical DNA repair defect paradigm, and how these processes shape tumor evolution and treatment resistance. Although genomic studies have catalogued millions of cancer-associated mutations, the goal is to understand the biological drivers responsible for generating these mutations. Emerging evidence shows that aberrant cellular signaling, metabolic rewiring, mitochondrial dysfunction, and oxidative stress actively contribute to genomic destabilization. Likewise, transcriptional network alterations, dysregulated signaling pathways, and aberrant chromatin remodeling are increasingly recognized in shaping the mutation processes.Recent advances in multi-omics technologies, high-resolution genome sequencing, metabolic profiling, and functional genomics now allow investigators to dissect the cellular pathways that produce mutational diversity. This Research Topic aims to integrate insights from molecular biology, cancer metabolism, genome maintenance, and systems biology to better understand the mechanistic underpinnings of mutation acquisition.This Research Topic will highlight studies addressing the molecular and cellular mechanisms that promote mutation generation and genomic instability in cancer. Areas of interest include, but are not limited to:• Mechanisms driving the mutations in cancer• Links between cellular metabolism, metabolic reprogramming, mitochondrial dysfunction, ROS production, and DNA damage• Mutational processes associated with tumor evolution and therapy resistance• Functional consequences of oncogenic variants that promote genomic instability• Interactions between chromatin structure, transcription, and epigenetic dysregulation• Multi-omics approaches to studying mutation generation – Computational/systems biology that link pathway alterations to mutational patterns• Inflammation‑ and immune‑driven mutagenic processes• Therapeutic strategies to target mutation-generating pathways Topic editors: Miltiadis Paliouras, Mark Trifiro Source: https://www.frontiersin.org/research-topics/79530/mechanisms-promoting-mutation-generation-in-cancer