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<p>Receptor tyrosine kinase (RTK) inhibitors have transformed the therapeutic landscape of gastrointestinal (GI) cancers, yet response heterogeneity and the emergence of resistance remain major clinical challenges. Liquid biopsy has emerged as a promising, noninvasive tool to capture tumor heterogeneity, monitor treatment dynamics, and potentially support precision therapy in real time. Across multiple clinical studies, circulating tumor DNA (ctDNA), cell-free DNA (cfDNA), microRNAs, circulating tumor cells (CTCs), extracellular vesicles (EVs), and methylated circulating DNA have demonstrated utility in three key domains, including predicting treatment response, stratifying prognosis, and detecting resistance. Its applications extend beyond correlation, providing potential predictive associations with treatment response, prognostic stratification of survival outcomes, and early detection of therapeutic resistance. Genomic alterations identified by liquid biopsy may predict benefit from RTK-targeted therapies in gastrointestinal stromal tumors (GIST), gastric cancer, colorectal cancer (CRC), and biliary tract malignancies, potentially enabling more refined patient selection than tissue-based testing alone. Moreover, baseline and dynamic changes in ctDNA and cfDNA levels correlate with survival outcomes across GI cancers, while complementary biomarkers such as circulating RNAs and EV-derived proteomic signatures provide additional prognostic resolution. Importantly, serial plasma profiling has revealed resistance mechanisms, including secondary RTK mutations, gene amplifications, and epigenetic alterations often months before clinical or radiologic progression, highlighting its possible role in adaptive treatment strategies. These findings suggest that liquid biopsy may serve not only as a correlative biomarker platform but also as an emerging clinical decision-support tool with potential implications for personalized RTK-targeted therapy in GI cancers. This article supports SDG 3 (Good Health and Well-Being) of the UN Agenda for Sustainable Development, presenting synthesis of state of the art evidence on liquid biopsy applications in gastrointestinal cancers.</p>

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Advancements in liquid biopsy for gastrointestinal cancers receiving RTK-targeted therapies: Predicting treatment response and monitoring disease progression

  • 期刊论文

  • 发表日期：

    2026年7月9日

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  • Amirhossein Molaei,
  • Farzaneh Kermani,
  • Pouya Goleij

摘要

Receptor tyrosine kinase (RTK) inhibitors have transformed the therapeutic landscape of gastrointestinal (GI) cancers, yet response heterogeneity and the emergence of resistance remain major clinical challenges. Liquid biopsy has emerged as a promising, noninvasive tool to capture tumor heterogeneity, monitor treatment dynamics, and potentially support precision therapy in real time. Across multiple clinical studies, circulating tumor DNA (ctDNA), cell-free DNA (cfDNA), microRNAs, circulating tumor cells (CTCs), extracellular vesicles (EVs), and methylated circulating DNA have demonstrated utility in three key domains, including predicting treatment response, stratifying prognosis, and detecting resistance. Its applications extend beyond correlation, providing potential predictive associations with treatment response, prognostic stratification of survival outcomes, and early detection of therapeutic resistance. Genomic alterations identified by liquid biopsy may predict benefit from RTK-targeted therapies in gastrointestinal stromal tumors (GIST), gastric cancer, colorectal cancer (CRC), and biliary tract malignancies, potentially enabling more refined patient selection than tissue-based testing alone. Moreover, baseline and dynamic changes in ctDNA and cfDNA levels correlate with survival outcomes across GI cancers, while complementary biomarkers such as circulating RNAs and EV-derived proteomic signatures provide additional prognostic resolution. Importantly, serial plasma profiling has revealed resistance mechanisms, including secondary RTK mutations, gene amplifications, and epigenetic alterations often months before clinical or radiologic progression, highlighting its possible role in adaptive treatment strategies. These findings suggest that liquid biopsy may serve not only as a correlative biomarker platform but also as an emerging clinical decision-support tool with potential implications for personalized RTK-targeted therapy in GI cancers. This article supports SDG 3 (Good Health and Well-Being) of the UN Agenda for Sustainable Development, presenting synthesis of state of the art evidence on liquid biopsy applications in gastrointestinal cancers.