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This review assesses traditional and emerging biomarkers supporting early detection, prognosis, and prediction of treatment resistance or sensitivity, emphasizing non-invasive liquid biopsy biomarkers (ctDNA, miRNAs, exosomes) and conventional genetic alterations (KRAS, BRAF, HER2). 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Earlier detection improves prognosis and supports more effective management.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"What types of biomarkers does the review compare?",{"text":68,"@type":64},"The review compares conventional biomarkers with emerging biomarkers, including non-invasive liquid biopsy markers (ctDNA, microRNAs, exosomes) and conventional genetic alterations (KRAS, BRAF, HER2).",{"name":70,"@type":61,"acceptedAnswer":71},"What limitations of liquid biopsy are discussed?",{"text":72,"@type":64},"Key limitations include cost-effectiveness, technological gaps in low-resource settings, and uncertain detection rates. 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Han 1, Mark R. Wakefield 2,3 and Yujiang Fang 1,2,3, *  \nAcademic Editor: AliZaidi  \nReceived: 21 July 2025  \nRevised: 12 August 2025  \nAccepted: 17 August 2025  \nPublished: 22 August 2025  \nCitation: Han, D.M.; Wakefield, M.R.; Fang, Y. Beyond Detection: Conventional and Emerging Biomarkers in Gastrointestinal Cancers. Cancers 2025, 17, 2725 . [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)cancers17172725  \nCopyright: © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://creativecommons.org/](https://creativecommons.org/)[ ](https://creativecommons.org/)[licenses/by/4.0/](licenses/by/4.0/)) .  \n1 Department of Microbiology, Immunology & Pathology, Des Moines University, West Des Moines, IA 50266, USA; [dmhan29@dmu.edu](dmhan29@dmu.edu)  \n2 Department of Surgery, University of Missouri School of Medicine, Columbia, MO 65212, USA; [wakefieldmr@health.missouri.edu](wakefieldmr@health.missouri.edu)  \n3 Ellis Fischel Cancer Center, University of Missouri School of Medicine, Columbia, MO 65212, USA  \n* [Correspondence: yujiang.fang@dmu.edu](Correspondence: yujiang.fang@dmu.edu); Tel.: +1-515-271-1435; Fax: +1-515-271-1543  \nSimple Summary  \nGastrointestinal (GI) cancers, including stomach, colon, and pancreas, are considered one of the most prevalent cancer types, majorly contributing to global cancer mortality. Often, the symptoms GI cancers are non-specific, leading to late diagnosis and detection. To tackle this challenge, scientists and physicians have been searching for “biomarkers.” Biomarkers are signals in blood, tissue, or even cancerous cells that tell us if cancer is present, resistance or sensitivity to certain drugs, and prognosis. This review explains and compares conventional biomarkers and new emerging biomarkers to highlight their benefits and disadvantages.  \nAbstract  \nGastrointestinal (GI) cancers, particularly colorectal and gastric cancers, majorly contribute to global cancer mortality due to frequent late-stage diagnosis and poor therapeutic response in advanced disease. Earlier detection of GI cancers is needed for a better prognosis. This review examines both traditional and emerging biomarkers that contribute significantly to early detection, prognostication, and prediction of therapeutic resistance or sensitivity. Specifically, we highlight the diagnostic utility of non-invasive liquid biopsy biomarkers such as circulating tumor DNA (ctDNA), microRNAs (miRNAs), and exosomes. Moreover, we discuss the prognostic and predictive value of conventional genetic alterations, including KRAS, BRAF, and HER2 . Although new findings have shown the advantages of liquid biopsy over colonoscopy, there are still limitations to the technique, such as cost-effectiveness, technological gaps in low-resource settings, and uncertain detection rates. Further studies are required to test the validity and accessibility of liquid biopsy and its biomarkers in order to advance personalized diagnosis and treatments for GI cancers. Such a study will be helpful for clinicians to better manage patients with GI cancers.  \nKeywords: Gastrointestinal cancer; colorectal cancer; gastric cancer; cancer biomarkers; precision medicine; molecular profiling; liquid biopsy; targeted therapy  \n1. Introduction  \nGastrointestinal (GI) cancers are cancers in the digestive tract and its associated organs. There were 353,802 new GI cases in the US, accounting for 17.8% of cancer incidents, in 2024. Furthermore, in the same year, 174,320 deaths from GI cancers were reported out of 611,720 total estimated deaths from cancers in the US, representing 28.5% of total estimated  \ndeaths [1] . Given its high incidence rate and mortality rates, there is a significant demand for fin","cbCaicOHJczTtx8s","https://ap.wps.com/l/cbCaicOHJczTtx8s","pdf",1081666,14,"English","# Introduction\n## Biomarkers and the need for early detection\n## Precision medicine and biomarker-guided therapy","[{\"question\":\"Why is early detection important in gastrointestinal (GI) cancers?\",\"answer\":\"Symptoms are often non-specific, contributing to late diagnosis and poorer outcomes. Earlier detection improves prognosis and supports more effective management.\"},{\"question\":\"What types of biomarkers does the review compare?\",\"answer\":\"The review compares conventional biomarkers with emerging biomarkers, including non-invasive liquid biopsy markers (ctDNA, microRNAs, exosomes) and conventional genetic alterations (KRAS, BRAF, HER2).\"},{\"question\":\"What limitations of liquid biopsy are discussed?\",\"answer\":\"Key limitations include cost-effectiveness, technological gaps in low-resource settings, and uncertain detection rates. The review emphasizes the need for further validation and accessibility studies.\"}]","Beyond Detection - Conventional and Emerging Biomarkers in Gastrointestinal Cancers | PDF",1790200226,35]