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Journal of Experimental & Clinical Cancer Research (2024) 43:239 [https://doi.org/10.1186/s13046-024-03141-5](https://doi.org/10.1186/s13046-024-03141-5)  \nJournal of Experimental & Clinical Cancer Research  \nREVIEW Open Access  \nConnecting the dots: investigating the link between environmental, genetic, and epigenetic influences in metabolomic alterations in oral squamous cell carcinoma  \nIshita Gupta 1,2, Fariba Badrzadeh 1,2, Yuri Tsentalovich3 and Daria A. Gaykalova 1,2,4,5*  \nAbstract  \nOral squamous cell carcinoma (OSCC) accounts for around 90% of all oral cancers and is the eighth most common cancer worldwide. Despite progress in managing OSCC, the overall prognosis remains poor, with a survival rate of around 50–60%, largely due to tumor size and recurrence. The challenges of late-stage diagnosis and limitations in current methods emphasize the urgent need for less invasive techniques to enable early detection and treatment, crucial for improving outcomes in this aggressive form of oral cancer. Research is currently aimed at unraveling tumor-specific metabolite profiles to identify candidate biomarkers as well as discover underlying pathways involved in the onset and progression of cancer that could be used as new targets for diagnostic and therapeutic purposes. Metabolomics is an advanced technological approach to identify metabolites in different sample types (biological fluids and tissues) . Since OSCC promotes metabolic reprogramming influenced by a combination of genetic predisposition and environmental factors, including tobacco and alcohol consumption, and viral infections, the identification of distinct metabolites through screening may aid in the diagnosis of this condition. Moreover, studies have shown the use of metabolites during the catalysis of epigenetic modification, indicating a link between epigenetics and metabolism. In this review, we will focus on the link between environmental, genetic, and epigenetic influences in metabolomic alterations in OSCC. In addition, we will discuss therapeutic targets of tumor metabolism, which may prevent oral tumor growth, metastasis, and drug resistance.  \nKeywords Metabolomics, Metabolism, Oral squamous cell carcinoma, Risk factors, Epigenetics  \n*Correspondence:  \nDaria A. Gaykalova  \n[dgaykalova@som. umaryland.edu](dgaykalova@som. umaryland.edu)  \n1Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA  \n2Department of Otorhinolaryngology-Head and Neck Surgery, Marlene & Stewart Greenebaum Comprehensive Cancer Center, University of Maryland Medical Center, Baltimore, MD, USA  \n3International tomography center CB RAS, Institutskaya str. 3a, Novosibirsk 630090, Russia  \n4Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA  \n5Institute for Genome Sciences, 670 West Baltimore Street, Baltimore, MD 21201, USA  \n© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/l](http://creativecommons.org/l)icenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ([http://creativecommons.org/publicdomain/zero/1.0/](http://creativecommons.org/publicdomain/zero/1.0/)) applie","cbCaifJX2rhKVYDe","https://ap.wps.com/l/cbCaifJX2rhKVYDe","pdf",4286480,32,"English","# Abstract\n# Introduction\n## OSCC burden and epidemiology\n## Risk factors and inflammatory pathways\n## Genetic and epigenetic progression\n# Keywords and correspondence","[{\"question\":\"Why is early detection of OSCC considered urgent?\",\"answer\":\"Late-stage diagnosis and limitations of current methods lead to poor outcomes. The review highlights an urgent need for less invasive techniques to enable early detection and treatment.\"},{\"question\":\"How does the review connect environmental, genetic, and epigenetic influences to OSCC metabolomics?\",\"answer\":\"It explains that OSCC promotes metabolic reprogramming shaped by genetic predisposition and environmental exposures such as tobacco and alcohol, alongside viral infections. It also links epigenetic modification catalysis with metabolite utilization, motivating investigation of combined influences on metabolomic alterations.\"},{\"question\":\"What is the potential value of metabolomics in this context?\",\"answer\":\"Metabolomics can identify distinct metabolites through screening to support diagnosis. The review also discusses using tumor metabolite-related pathways to define therapeutic targets aimed at reducing tumor growth, metastasis, and drug resistance.\"}]","Connecting the dots: investigating the link between environmental, genetic, and epigenetic influences in metabolomic alterations in oral squamous cell carcinoma | PDF",1789997837,81]