Circulating tumor cell markers for early detection and drug resistance assessment through liquid biopsy - Review

Sep 23, 2026

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Review of circulating tumor cell (CTC) markers highlights how CTCs, shed from primary tumors or metastases into the bloodstream, support understanding of metastasis, tumor evolution during therapy, and emergence of chemo- and/or radio-resistance. The review focuses on epithelial-to-mesenchymal transition (EMT)-derived CTC formation, the marker shift from EpCAM to mesenchymal markers such as vimentin, and major marker sets used for identification, including EpCAM, CD44/CD24, cytokeratins, HER2/neu, and vimentin. It also discusses immune-based isolation and enrichment approaches and the clinical potential for early detection and personalized treatment to halt disease progression and multidrug resistance.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages17

Reading Time43 min

AccessFree to download

1 Introduction

Cancer burden and therapeutic challenges

Key concepts and CTC biology

EMT and marker transitions

Common CTC surface markers

Isolation and enrichment approaches

Immune-based techniques

Clinical relevance

Early detection and drug resistance assessment

TYPE Review PUBLISHED 07 April 2025 DOI 10.3389/fonc.2025.1494723 OPEN ACCESS EDITED BY Sharon R. Pine, University of Colorado Anschutz Medical Campus, United States REVIEWED BY Michele Zanoni, Scientiﬁc Institute of Romagna for the Study and Treatment of Tumors (IRCCS), Italy Giulia Gallerani, University of Bologna, Italy *CORRESPONDENCE N. Rajendra Prasad [drprasadnr@gmail.com](drprasadnr@gmail.com) RECEIVED 11 September 2024 ACCEPTED 18 March 2025 PUBLISHED 07 April 2025 CITATION Yadav P, Rajendrasozhan S, Lajimi RH, Patel RR, Heymann D and Prasad NR (2025) Circulating tumor cell markers for early detection and drug resistance assessment through liquid biopsy. Front. Oncol. 15:1494723 . doi: 10.3389/fonc.2025.1494723 COPYRIGHT © 2025 Yadav, Rajendrasozhan, Lajimi, Patel, Heymann and Prasad. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Circulating tumor cell markers for early detection and drug resistance assessment through liquid biopsy Priya Yadav 1, Saravanan Rajendrasozhan 2,3, Ramzi Hadj Lajimi 2,3, Raja Ramadevi Patel 3,4, Dominique Heymann 5,6,7 and N. Rajendra Prasad 1* 1 Department of Biochemistry and Biotechnology, Annamalai University, Chidambaram, Tamil Nadu, India, 2 Department of Chemistry, College of Science, University of Ha’ il, Ha’ il, Saudi Arabia, 3 Medical and Diagnostic Research Centre, University of Ha’ il, Ha’ il, Saudi Arabia, 4 Department of Biology, College of Science, University of Ha’ il, Ha ’ il, Saudi Arabia, 5 Nantes Universite´, CNRS, US2B, UMR 6286, Nantes, France, 6 Institut de Cance´ rologie de l’Ouest, Tumor Heterogeneity and Precision Medecine Laboratory, Saint-Herblain, France, 7 Medical School, University of Shefﬁeld, Shefﬁeld, United Kingdom Circulating tumor cells (CTCs) are cancerous cells that extravasate from the primary tumor or metastatic foci and travel through the bloodstream to distant organs. CTCs provide crucial insights into cancer metastasis, the evolution of tumor genotypes during treatment, and the development of chemo- and/or radio-resistance during disease progression. The process of Epithelial-tomesenchymal transition (EMT) plays a key role in CTCs formation, as this process enhances cell ’s migration properties and is often associated with increased invasiveness thereby leading to chemotherapy resistance. During the EMT process, tumor cells lose epithelial markers like EpCAM and acquire mesenchymal markers such as vimentin driven by transcription factors like Snail and Twist. CTCs are typically identiﬁed using speciﬁc cell surface markers, which vary depending on the cancer type. Common markers include EpCAM, used for epithelial cancers; CD44 and CD24, which are associated with cancer stem cells; and cytokeratins, such as CK8 and CK18 . Other markers like HER2/neu and vimentin can also be used to target CTCs in speciﬁc cancer types and stages. Commonly, immune-based isolation techniques are being implemented for the isolation and enrichment of CTCs. This review emphasizes the clinical relevance of CTCs, particularly in understanding drug resistance mechanisms, and underscores the importance of EMT-derived CTCs in multidrug resistance (MDR) . Moreover, the review also discusses CTCs-speciﬁc surface markers that are crucial for their isolation and enrichment. Ultimately, the EMT-speciﬁc markers found in CTCs could provide signiﬁcant information to halt the disease progression and enable personalized therapies. KEYWORDS liquid biopsies, circulating tumor cells, multidrug resistance, tumor plasticity, ear

FAQs

Why are circulating tumor cells (CTCs) important for cancer management?

CTCs provide insights into metastasis, tumor genotype evolution during treatment, and development of chemo- and radio-resistance, helping assess disease progression and therapeutic response.

How does EMT contribute to CTC formation and drug resistance?

During EMT, tumor cells downregulate epithelial markers such as EpCAM and upregulate mesenchymal markers like vimentin, driven by transcription factors including Snail and Twist, which enhances migration and invasiveness and is linked to chemotherapy resistance.

Which CTC surface markers are commonly discussed for identification?

Markers include EpCAM for epithelial cancers; CD44 and CD24 for cancer stem cell–associated profiles; cytokeratins such as CK8 and CK18; and additional markers like HER2/neu and vimentin depending on cancer type and stage.

Sep 23, 2026

Uploaded by Mia