Deciphering Multilevel Mechanisms of Oral Carcinogenesis through Multi-Omics and Microenvironment Profiling

Oral cancer biology is a rapidly advancing field that seeks to understand the origins, progression, and clinical management of malignancies arising in the oral cavity. Despite significant clinical advances, oral cancer remains a major health challenge worldwide, particularly due to its frequent evolution from oral potentially malignant disorders (OPMDs) such as leukoplakia, erythroplakia, and oral submucous fibrosis. While early detection is key to improving outcomes, our understanding of the molecular drivers behind the malignant transformation of OPMDs is incomplete. Contemporary research often isolates genetic, epigenetic, or histological features, missing the intricate interplay of multilevel alterations—including genomic instability, epigenetic reprogramming, transcriptional changes, metabolic adaptation, and the evolving tumor microenvironment—that contribute to cancer progression. Recent multi-omics studies have begun to reveal a more nuanced landscape, uncovering complex regulatory networks and uncovering cellular heterogeneity during the transition from premalignancy to invasive oral cancer. However, there remains a pressing need for integrated approaches that combine comprehensive molecular profiling with functional and clinical validation, which is essential for the discovery of actionable biomarkers and effective preventive strategies. Current gaps include a lack of reliable predictive tools, insufficient understanding of tumor–immune crosstalk, and limited clinical translation of basic research findings.This Research Topic aims to accelerate the understanding of the multilevel mechanisms underlying the malignant transformation of OPMDs and extend these discoveries into clinical innovations. By fostering an interdisciplinary platform, the topic will spotlight studies that employ integrative multi omics analyses, advanced cellular and animal models, and state of the art imaging and computational techniques. Submissions are particularly encouraged to address how cellular intrinsic regulatory networks interact with the tumor microenvironment and how these dynamic processes can be leveraged for the development of new diagnostic, prognostic, and interception strategies. The objective is to unravel the complexities of oral cancer progression, identify early events in the malignant continuum, and provide a foundation for improved patient stratification and targeted interventions.To gather further insights into the biological and translational facets of oral cancer progression from OPMDs, this Research Topic is focused on original studies, reviews, and methodologies that extend from mechanistic investigation to early clinical translation. We welcome articles addressing, but not limited to, the following themes:o Integration of multi omics data to identify drivers of malignant transformation in OPMDs, with functional validationo Dissection of the tumor microenvironment and immune regulation governing premalignant progressiono Single cell and spatial multi omics approaches to resolve cellular heterogeneity and evolutionary dynamics in OPMDso Exploration of metabolic reprogramming and the role of the microbiome in oral premalignant lesionso Development and validation of diagnostic, prognostic, or predictive biomarkers, including those utilizing liquid biopsy, radiomics, or AI-assisted approachesAppendix: Article types welcomed include Original Research, Reviews, Methods, Perspectives, and Brief Research Reports. Studies that integrate robust mechanistic insights with experimental or clinical validation will be prioritized, while purely computational analyses without validation will be considered out of scope. Topic editors: Yuehong Shen, Yicun Li, Li Wu Zheng, Petar Ozretić Source: https://www.frontiersin.org/research-topics/85673/deciphering-multilevel-mechanisms-of-oral-carcinogenesis-through-multi-omics-and-microenvironment-profiling