{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T22:54:16Z","timestamp":1783464856301,"version":"3.55.0"},"reference-count":122,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T00:00:00Z","timestamp":1767052800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science Centre, Poland","award":["2023\/50\/E\/NZ5\/00507"],"award-info":[{"award-number":["2023\/50\/E\/NZ5\/00507"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Lung cancer, as one of the most prevalent and lethal malignancies, requires immediate and effective therapeutic solutions. Therefore, additional innovative methods are continually sought to achieve optimal treatment outcomes. Various markers are used to select the most effective therapies, assess clinical responses, and facilitate follow-up care for the patients. Circulating tumor cells (CTCs) remain a valuable biomarker in clinical management of cancer patients due to the range of information they provide and their high prognostic and predictive potential in monitoring anticancer therapy. CTCs constitute a heterogeneous population of cancer cells that undergo an epithelial-to-mesenchymal transition (EMT), are shed from the tumor mass, and migrate through the peripheral blood, ultimately causing metastases. In this literature review, we focus on the biological, biochemical, and biophysical properties of CTCs, specifically from the perspective of the design of CTC enumeration technologies. Furthermore, we combine the available data on the application of CTC count in monitoring various treatment modalities in lung cancer, including radiotherapy, chemotherapy, tyrosine kinase inhibitors, and immunotherapy. Although many published reports indicate that an increased number of CTCs in blood samples of lung cancer patients correlates with worse treatment outcomes, several limitations hinder the widespread usage of CTCs in the clinical setting.<\/jats:p>","DOI":"10.3390\/ijms27010384","type":"journal-article","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T15:30:32Z","timestamp":1767195032000},"page":"384","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Circulating Tumor Cells for the Monitoring of Lung Cancer Therapies"],"prefix":"10.3390","volume":"27","author":[{"given":"Maja","family":"Chrzempiec","sequence":"first","affiliation":[{"name":"Department of Cancer Immunology, Poznan University of Medical Sciences, Rokietnicka Street 8, 60-806 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0357-9284","authenticated-orcid":false,"given":"Urszula","family":"Oleksiewicz","sequence":"additional","affiliation":[{"name":"Department of Cancer Immunology, Poznan University of Medical Sciences, Rokietnicka Street 8, 60-806 Poznan, Poland"},{"name":"Department of Diagnostics and Cancer Immunology, Greater Poland Cancer Center, Garbary Street 15, 61-866 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,30]]},"reference":[{"key":"ref_1","unstructured":"Ferlay, J., Ervik, M., Lam, F., Laversanne, M., Colombet, M., Mery, L., Pi\u00f1eros, M., Znaor, A., Soerjomataram, I., and Bray, F. (2024). Global Cancer Observatory: Cancer Today, International Agency for Research on Cancer. Available online: https:\/\/gco.iarc.who.int\/today."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1001\/jamaoncol.2021.6987","article-title":"Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life Years for 29 Cancer Groups From 2010 to 2019","volume":"8","author":"Kocarnik","year":"2022","journal-title":"JAMA Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/s12943-023-01740-y","article-title":"Lung Cancer Immunotherapy: Progress, Pitfalls, and Promises","volume":"22","author":"Lahiri","year":"2023","journal-title":"Mol. Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1186\/s13045-024-01640-8","article-title":"Global Burden of Cancer and Associated Risk Factors in 204 Countries and Territories, 1980\u20132021: A Systematic Analysis for the GBD 2021","volume":"17","author":"Wu","year":"2024","journal-title":"J. Hematol. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"461","DOI":"10.2147\/CMAR.S506630","article-title":"Multimodal Framework in Lung Cancer Management: Integrating Liquid Biopsy with Traditional Diagnostic Techniques","volume":"17","author":"Qi","year":"2025","journal-title":"CMAR"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Casagrande, G.M.S., Silva, M.d.O., Reis, R.M., and Leal, L.F. (2023). Liquid Biopsy for Lung Cancer: Up-to-Date and Perspectives for Screening Programs. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24032505"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Jiang, S.-S., Deng, B., Feng, Y.-G., Qian, K., Tan, Q.-Y., and Wang, R.-W. (2019). Circulating Tumor Cells Prior to Initial Treatment Is an Important Prognostic Factor of Survival in Non-Small Cell Lung Cancer: A Meta-Analysis and System Review. BMC Pulm. Med., 19.","DOI":"10.1186\/s12890-019-1029-x"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Wang, J., Wang, K., Xu, J., Huang, J., and Zhang, T. (2013). Prognostic Significance of Circulating Tumor Cells in Non-Small-Cell Lung Cancer Patients: A Meta-Analysis. PLoS ONE, 8, Correction in PLoS ONE\u00a02014, 9. https:\/\/doi.org\/10.1371\/annotation\/6633ed7f-a10c-4f6d-9d1d-9c1245822eb7.","DOI":"10.1371\/annotation\/6633ed7f-a10c-4f6d-9d1d-9c1245822eb7"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"8429","DOI":"10.7314\/APJCP.2014.15.19.8429","article-title":"Prognostic Significance of Circulating Tumor Cells in Small--Cell Lung Cancer Patients: A Meta-Analysis","volume":"15","author":"Zhang","year":"2014","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1111\/jebm.12606","article-title":"The Detection of Circulating Tumor Cells Indicates Poor Therapeutic Efficacy and Prognosis in Patients with Nonsmall Cell Lung Cancer: A Systematic Review and Meta-Analysis","volume":"17","author":"Wang","year":"2024","journal-title":"J. Evid. Based Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"220151","DOI":"10.1183\/16000617.0151-2022","article-title":"Circulating Tumour Cells in Patients with Lung Cancer Universally Indicate Poor Prognosis","volume":"31","author":"Jin","year":"2022","journal-title":"Eur. Respir. Rev."},{"key":"ref_12","first-page":"146","article-title":"A Case of Cancer in Which Cells Similar to Those in the Tumors Were Seen in the Blood after Death","volume":"14","author":"Ashworth","year":"1896","journal-title":"Austral. Med. J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1038\/s41392-021-00817-8","article-title":"Circulating Tumor Cells: Biology and Clinical Significance","volume":"6","author":"Lin","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"25ra23","DOI":"10.1126\/scitranslmed.3000403","article-title":"Isolation and Characterization of Circulating Tumor Cells from Patients with Localized and Metastatic Prostate Cancer","volume":"2","author":"Stott","year":"2010","journal-title":"Sci. Transl. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.semcancer.2020.12.014","article-title":"Causes, Effects, and Clinical Implications of Perturbed Patterns within the Cancer Epigenome","volume":"83","author":"Oleksiewicz","year":"2022","journal-title":"Semin. Cancer Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1007\/978-3-319-55947-6_12","article-title":"Mesenchymal-Epithelial Transition and Circulating Tumor Cells in Small Cell Lung Cancer","volume":"994","author":"Hamilton","year":"2017","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Harris, A.R., Perez, M.J., and Munson, J.M. (2018). Docetaxel Facilitates Lymphatic-Tumor Crosstalk to Promote Lymphangiogenesis and Cancer Progression. BMC Cancer, 18.","DOI":"10.1186\/s12885-018-4619-8"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Han, M., Watts, J.A., Jamshidi-Parsian, A., Nadeem, U., Sarimollaoglu, M., Siegel, E.R., Zharov, V.P., and Galanzha, E.I. (2020). In Vivo Lymphatic Circulating Tumor Cells and Progression of Metastatic Disease. Cancers, 12.","DOI":"10.3390\/cancers12102866"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1146\/annurev-bioeng-062117-120947","article-title":"Circulating Tumor Cells: Diagnostic and Therapeutic Applications","volume":"20","author":"Lin","year":"2018","journal-title":"Annu. Rev. Biomed. Eng."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1186\/s13046-024-03026-7","article-title":"Liquid Biopsy Techniques and Lung Cancer: Diagnosis, Monitoring and Evaluation","volume":"43","author":"Ren","year":"2024","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_21","first-page":"269","article-title":"A Potential \u201cAnti-Warburg Effect\u201d in Circulating Tumor Cell-Mediated Metastatic Progression?","volume":"16","author":"Jiang","year":"2023","journal-title":"Aging Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"9986","DOI":"10.1073\/pnas.1803884115","article-title":"Functional Profiling of Circulating Tumor Cells with an Integrated Vortex Capture and Single-Cell Protease Activity Assay","volume":"115","author":"Dhar","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Canciello, A., Cerver\u00f3-Varona, A., Peserico, A., Mauro, A., Russo, V., Morrione, A., Giordano, A., and Barboni, B. (2022). \u201cIn Medio Stat Virtus\u201d: Insights into Hybrid E\/M Phenotype Attitudes. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.1038841"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Pasani, S., Sahoo, S., and Jolly, M.K. (2020). Hybrid E\/M Phenotype(s) and Stemness: A Mechanistic Connection Embedded in Network Topology. J. Clin. Med., 10.","DOI":"10.1101\/2020.10.18.341271"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1038\/s41586-020-03046-1","article-title":"Fat1 Deletion Promotes Hybrid EMT State, Tumour Stemness and Metastasis","volume":"589","author":"Pastushenko","year":"2021","journal-title":"Nature"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"R46","DOI":"10.1186\/bcr2333","article-title":"Stem Cell and Epithelial-Mesenchymal Transition Markers Are Frequently Overexpressed in Circulating Tumor Cells of Metastatic Breast Cancer Patients","volume":"11","author":"Aktas","year":"2009","journal-title":"Breast Cancer Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1158\/1535-7163.MCT-18-0584","article-title":"Circulating Tumor Cells with Stemness and Epithelial-to-Mesenchymal Transition Features Are Chemoresistant and Predictive of Poor Outcome in Metastatic Breast Cancer","volume":"18","author":"Papadaki","year":"2019","journal-title":"Mol. Cancer Ther."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"104237","DOI":"10.1016\/j.ebiom.2022.104237","article-title":"Circulating Tumor Cell Isolation for Cancer Diagnosis and Prognosis","volume":"83","author":"Deng","year":"2022","journal-title":"eBioMedicine"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1186\/s12943-024-02069-w","article-title":"Cancer, Metastasis, and the Epigenome","volume":"23","author":"Kiri","year":"2024","journal-title":"Mol. Cancer"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1038\/s41392-024-01938-6","article-title":"Circulating Tumor Cells: From New Biological Insights to Clinical Practice","volume":"9","author":"Gu","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_31","first-page":"25","article-title":"Shear Stress Activates ATOH8 via Autocrine VEGF Promoting Glycolysis Dependent-Survival of Colorectal Cancer Cells in the Circulation","volume":"39","author":"Huang","year":"2020","journal-title":"J. Exp. Clin. Cancer Res. CR"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"jcs259586","DOI":"10.1242\/jcs.259586","article-title":"Fluid Shear Stress Regulates the Survival of Circulating Tumor Cells via Nuclear Expansion","volume":"135","author":"Xu","year":"2022","journal-title":"J. Cell Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s13058-018-1071-2","article-title":"Hydrodynamic Shear Stress Promotes Epithelial-Mesenchymal Transition by Downregulating ERK and GSK3\u03b2 Activities","volume":"21","author":"Choi","year":"2019","journal-title":"Breast Cancer Res."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Xin, Y., Li, K., Yang, M., and Tan, Y. (2020). Fluid Shear Stress Induces Emt of Circulating Tumor Cells via Jnk Signaling in Favor of Their Survival during Hematogenous Dissemination. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21218115"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"216870","DOI":"10.1016\/j.canlet.2024.216870","article-title":"Circulating Tumor Cells with Metastasis-Initiating Competence Survive Fluid Shear Stress during Hematogenous Dissemination through CXCR4-PI3K\/AKT Signaling","volume":"590","author":"Xin","year":"2024","journal-title":"Cancer Lett."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1016\/j.cell.2014.07.013","article-title":"Circulating Tumor Cell Clusters Are Oligoclonal Precursors of Breast Cancer Metastasis","volume":"158","author":"Aceto","year":"2014","journal-title":"Cell"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1038\/s41586-019-0915-y","article-title":"Neutrophils Escort Circulating Tumour Cells to Enable Cell Cycle Progression","volume":"566","author":"Szczerba","year":"2019","journal-title":"Nature"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1007\/s10555-017-9681-1","article-title":"Platelets, Circulating Tumor Cells, and the Circulome","volume":"36","author":"Lam","year":"2017","journal-title":"Cancer Metastasis Rev."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1038\/ncb2548","article-title":"Classifying Collective Cancer Cell Invasion","volume":"14","author":"Friedl","year":"2012","journal-title":"Nat. Cell Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1016\/j.ccr.2011.09.009","article-title":"Direct Signaling Between Platelets and Cancer Cells Induces an Epithelial-Mesenchymal-Like Transition and Promotes Metastasis","volume":"20","author":"Labelle","year":"2011","journal-title":"Cancer Cell"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Garrido-Navas, C., Miguel-P\u00e9rez, D.d., Exposito-Hernandez, J., Bayarri, C., Amezcua, V., Ortigosa, A., Valdivia, J., Guerrero, R., Puche, J.L.G., and Lorente, J.A. (2019). Cooperative and Escaping Mechanisms between Circulating Tumor Cells and Blood Constituents. Cells, 8.","DOI":"10.3390\/cells8111382"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"C743","DOI":"10.1152\/ajpcell.00250.2007","article-title":"Two-Dimensional Kinetics of Beta 2-Integrin and ICAM-1 Bindings between Neutrophils and Melanoma Cells in a Shear Flow","volume":"294","author":"Liang","year":"2008","journal-title":"Am. J. Physiol.-Cell Physiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1158\/2159-8290.CD-15-1157","article-title":"Neutrophils Suppress Intraluminal NK Cell-Mediated Tumor Cell Clearance and Enhance Extravasation of Disseminated Carcinoma Cells","volume":"6","author":"Spiegel","year":"2016","journal-title":"Cancer Discov."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3446","DOI":"10.1172\/JCI67484","article-title":"Neutrophil Extracellular Traps Sequester Circulating Tumor Cells and Promote Metastasis","volume":"123","author":"Spicer","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"5397","DOI":"10.1007\/s13277-015-4349-3","article-title":"Circulating Tumor-Associated Neutrophils (cTAN) Contribute to Circulating Tumor Cell Survival by Suppressing Peripheral Leukocyte Activation","volume":"37","author":"Zhang","year":"2016","journal-title":"Tumour Biol. J. Int. Soc. Oncodevelopm. Biol. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/nature14282","article-title":"IL17-Producing \u0393\u03b4 T Cells and Neutrophils Conspire to Promote Breast Cancer Metastasis","volume":"522","author":"Coffelt","year":"2015","journal-title":"Nature"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Sprouse, M.L., Welte, T., Boral, D., Liu, H.N., Yin, W., Vishnoi, M., Goswami-Sewell, D., Li, L., Pei, G., and Jia, P. (2019). PMN-MDSCs Enhance CTC Metastatic Properties through Reciprocal Interactions via ROS\/Notch\/Nodal Signaling. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20081916"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1164\/rccm.201708-1707OC","article-title":"Circulating and Tumor Myeloid-Derived Suppressor Cells in Resectable Non-Small Cell Lung Cancer","volume":"198","author":"Yamauchi","year":"2018","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Hurtado, P., Mart\u00ednez-Pena, I., and Pi\u00f1eiro, R. (2020). Dangerous Liaisons: Circulating Tumor Cells (Ctcs) and Cancer-Associated Fibroblasts (Cafs). Cancers, 12.","DOI":"10.3390\/cancers12102861"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"4294","DOI":"10.1038\/s41467-023-39762-1","article-title":"Cancer-Associated Fibroblast Classification in Single-Cell and Spatial Proteomics Data","volume":"14","author":"Cords","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1038\/ncb1658","article-title":"Fibroblast-Led Collective Invasion of Carcinoma Cells with Differing Roles for RhoGTPases in Leading and Following Cells","volume":"9","author":"Gaggioli","year":"2007","journal-title":"Nat. Cell Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/S0002-9440(10)64706-2","article-title":"Isolation by Size of Epithelial Tumor Cells: A New Method for the Immunomorphological and Molecular Characterization of Circulating Tumor Cells","volume":"156","author":"Vona","year":"2000","journal-title":"Am. J. Pathol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/s13045-019-0735-4","article-title":"Technologies for Circulating Tumor Cell Separation from Whole Blood","volume":"12","author":"Lee","year":"2019","journal-title":"J. Hematol. Oncol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1182\/blood.V56.5.866.866","article-title":"Morphometry of Human Leukocytes","volume":"56","author":"Shih","year":"1980","journal-title":"Blood"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1002\/1878-0261.12802","article-title":"Defining the Dimensions of Circulating Tumor Cells in a Large Series of Breast, Prostate, Colon, and Bladder Cancer Patients","volume":"15","author":"Mendelaar","year":"2020","journal-title":"Mol. Oncol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2911","DOI":"10.1007\/s00432-019-03040-9","article-title":"Vimentin Expression in Circulating Tumor Cells (CTCs) Associated with Liver Metastases Predicts Poor Progression-Free Survival in Patients with Advanced Lung Cancer","volume":"145","author":"Wang","year":"2019","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"8152","DOI":"10.1158\/1078-0432.CCR-04-1110","article-title":"Circulating Tumor Cells in Patients with Breast Cancer Dormancy","volume":"10","author":"Meng","year":"2004","journal-title":"Clin. Cancer Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"5233","DOI":"10.1158\/1078-0432.CCR-10-1449","article-title":"M30 Neoepitope Expression in Epithelial Cancer: Quantification of Apoptosis in Circulating Tumor Cells by CellSearch Analysis","volume":"16","author":"Rossi","year":"2010","journal-title":"Clin. Cancer Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1007\/s12032-016-0875-0","article-title":"CTC Clusters in Cancer Progression and Metastasis","volume":"34","author":"Fabisiewicz","year":"2017","journal-title":"Med. Oncol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1002\/1878-0261.13369","article-title":"Collective Directional Migration Drives the Formation of Heteroclonal Cancer Cell Clusters","volume":"17","author":"Palmiero","year":"2023","journal-title":"Mol. Oncol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1007\/s10555-023-10124-z","article-title":"How Circulating Tumor Cluster Biology Contributes to the Metastatic Cascade: From Invasion to Dissemination and Dormancy","volume":"42","author":"Nasr","year":"2023","journal-title":"Cancer Metastasis Rev."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"4867","DOI":"10.1038\/s41467-021-25189-z","article-title":"ICAM1 Initiates CTC Cluster Formation and Trans-Endothelial Migration in Lung Metastasis of Breast Cancer","volume":"12","author":"Taftaf","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.bj.2019.11.002","article-title":"Bring along Your Friends: Homotypic and Heterotypic Circulating Tumor Cell Clustering to Accelerate Metastasis","volume":"43","author":"Aceto","year":"2020","journal-title":"Biomed. J."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1007\/978-1-4939-7144-2_24","article-title":"Circulating Tumor Cells: Markers and Methodologies for Enrichment and Detection","volume":"1634","author":"Cubero","year":"2017","journal-title":"Methods Mol. Biol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/s12943-022-01505-z","article-title":"Liquid Biopsy in Lung Cancer: Significance in Diagnostics, Prediction, and Treatment Monitoring","volume":"21","author":"Li","year":"2022","journal-title":"Mol. Cancer"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1186\/s13045-022-01351-y","article-title":"Liquid Biopsy: Current Technology and Clinical Applications","volume":"15","author":"Nikanjam","year":"2022","journal-title":"J. Hematol. Oncol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"594","DOI":"10.21037\/tlcr-22-742","article-title":"Current and Future Applications of Liquid Biopsy in Non-Small-Cell Lung Cancer\u2014A Narrative Review","volume":"12","author":"Tomasik","year":"2023","journal-title":"Transl. Lung Cancer Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"6897","DOI":"10.1158\/1078-0432.CCR-04-0378","article-title":"Tumor Cells Circulate in the Peripheral Blood of All Major Carcinomas but Not in Healthy Subjects or Patients with Nonmalignant Diseases","volume":"10","author":"Allard","year":"2004","journal-title":"Clin. Cancer Res."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Antolovic, D., Galindo, L., Carstens, A., Rahbari, N., B\u00fcchler, M.W., Weitz, J., and Koch, M. (2010). Heterogeneous Detection of Circulating Tumor Cells in Patients with Colorectal Cancer by Immunomagnetic Enrichment Using Different EpCAM-Specific Antibodies. BMC Biotechnol., 10.","DOI":"10.1186\/1472-6750-10-35"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"4193","DOI":"10.1021\/acsami.9b16385","article-title":"Rapid Label-Free Isolation of Circulating Tumor Cells from Patients\u2019 Peripheral Blood Using Electrically Charged Fe3O4 Nanoparticles","volume":"12","author":"Wu","year":"2020","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"32851","DOI":"10.1038\/srep32851","article-title":"Application of Optically-Induced-Dielectrophoresis in Microfluidic System for Purification of Circulating Tumour Cells for Gene Expression Analysis- Cancer Cell Line Model","volume":"6","author":"Chiu","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1186\/s13046-024-03149-x","article-title":"Identification of Circulating Tumor Cells Captured by the FDA-Cleared Parsortix\u00ae PC1 System from the Peripheral Blood of Metastatic Breast Cancer Patients Using Immunofluorescence and Cytopathological Evaluations","volume":"43","author":"Ciccioli","year":"2024","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1038\/s41378-020-0131-9","article-title":"AFM-Compatible Microfluidic Platform for Affinity-Based Capture and Nanomechanical Characterization of Circulating Tumor Cells","volume":"6","author":"Deliorman","year":"2020","journal-title":"Microsyst. Nanoeng."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Szerenyi, D., Jarvas, G., and Guttman, A. (2025). Multifaceted Approaches in Epithelial Cell Adhesion Molecule-Mediated Circulating Tumor Cell Isolation. Molecules, 30.","DOI":"10.3390\/molecules30050976"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1586\/14737159.2016.1123095","article-title":"Challenges for CTC-Based Liquid Biopsies: Low CTC Frequency and Diagnostic Leukapheresis as a Potential Solution","volume":"16","author":"Stoecklein","year":"2016","journal-title":"Expert Rev. Mol. Diagn"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"386","DOI":"10.2353\/ajpath.2007.070152","article-title":"Epithelial Cell Adhesion Molecule: More than a Carcinoma Marker and Adhesion Molecule","volume":"171","author":"Trzpis","year":"2007","journal-title":"Am. J. Pathol."},{"key":"ref_77","first-page":"461","article-title":"Circulating Tumor Cells Isolation: \u201cThe Post-EpCAM Era\u201d","volume":"27","author":"Raimondi","year":"2015","journal-title":"Chin. J. Cancer Res."},{"key":"ref_78","first-page":"3455","article-title":"Immunobead-PCR: A Technique for the Detection of Circulating Tumor Cells Using Immunomagnetic Beads and the Polymerase Chain Reaction","volume":"53","author":"Hardingham","year":"1993","journal-title":"Cancer Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/j.molonc.2015.12.002","article-title":"Challenges in Circulating Tumor Cell Detection by the CellSearch System","volume":"10","author":"Andree","year":"2016","journal-title":"Mol. Oncology"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Gorges, T.M., Tinhofer, I., Drosch, M., R\u00f6se, L., Zollner, T.M., Krahn, T., and Ahsen, O. (2012). von Circulating Tumour Cells Escape from EpCAM-Based Detection Due to Epithelial-to-Mesenchymal Transition. BMC Cancer, 12.","DOI":"10.1186\/1471-2407-12-178"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1849454418782617","DOI":"10.1177\/1849454418782617","article-title":"Improved Ovarian Cancer EMT-CTC Isolation by Immunomagnetic Targeting of Epithelial EpCAM and Mesenchymal N-Cadherin","volume":"7","author":"Po","year":"2018","journal-title":"J. Circ. Biomark."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1887","DOI":"10.7150\/thno.16358","article-title":"Targeting Negative Surface Charges of Cancer Cells by Multifunctional Nanoprobes","volume":"6","author":"Chen","year":"2016","journal-title":"Theranostics"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1039\/C3LC50625H","article-title":"Technologies for Label-Free Separation of Circulating Tumor Cells: From Historical Foundations to Recent Developments","volume":"14","author":"Jin","year":"2014","journal-title":"Lab Chip"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1073\/pnas.92.3.860","article-title":"Separation of Human Breast Cancer Cells from Blood by Differential Dielectric Affinity","volume":"92","author":"Becker","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_85","first-page":"1529","article-title":"Liquid Biopsy of Circulating Tumor Cells: From Isolation, Enrichment, and Genome Sequencing to Clinical Applications","volume":"40","author":"Tan","year":"2025","journal-title":"Histol. Histopathol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1038\/nprot.2014.044","article-title":"Microfluidic, Marker-Free Isolation of Circulating Tumor Cells from Blood Samples","volume":"9","author":"Karabacak","year":"2014","journal-title":"Nat. Protoc."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"10936","DOI":"10.1038\/s41598-017-11119-x","article-title":"Monolithic Chip for High-Throughput Blood Cell Depletion to Sort Rare Circulating Tumor Cells","volume":"7","author":"Fachin","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Xu, L., Mao, X., Imrali, A., Syed, F., Mutsvangwa, K., Berney, D., Cathcart, P., Hines, J., Shamash, J., and Lu, Y.J. (2015). Optimization and Evaluation of a Novel Size Based Circulating Tumor Cell Isolation System. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0138032"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"2014","DOI":"10.1002\/1878-0261.13705","article-title":"A Comparative Study of Circulating Tumor Cell Isolation and Enumeration Technologies in Lung Cancer","volume":"19","author":"Saini","year":"2025","journal-title":"Mol. Oncol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2500351","DOI":"10.1002\/smsc.202500351","article-title":"Nanoscale Analysis beyond Imaging by Atomic Force Microscopy: Molecular Perspectives on Oncology and Neurodegeneration","volume":"5","author":"Marcuello","year":"2025","journal-title":"Small Sci."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Sugai, K., Mori, T., Bilal, T., Furukawa, A., Sekine, Y., Kobayashi, N., Kikuchi, S., Goto, Y., Ichimura, H., and Masuda, T. (2024). Detection of Circulating Tumor Cells in Patients with Lung Cancer Using a Rare Cell Sorter: A Pilot Study. BMC Cancer, 24.","DOI":"10.1186\/s12885-024-12945-9"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"12060","DOI":"10.7150\/thno.48918","article-title":"Circulating Tumor Cells in Hepatocellular Carcinoma: Single-Cell Based Analysis, Preclinical Models, and Clinical Applications","volume":"10","author":"Zhang","year":"2020","journal-title":"Theranostics"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Liang, W., Xu, Z., Kong, F., Huang, X., Xiao, Y., Zhou, W., Ye, S., and Ye, Q. (2022). Circulating Tumour Cell Combined with DNA Methylation for Early Detection of Hepatocellular Carcinoma. Front. Genet., 13.","DOI":"10.3389\/fgene.2022.1065693"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1002\/cncy.22690","article-title":"Evaluating Diff-Quik Cytology Smears for Large-panel Mutation Testing in Lung Cancer\u2014Predicting DNA Content and Success with Low-malignant-cellularity Samples","volume":"131","author":"Fielding","year":"2023","journal-title":"Cancer Cytopathol."},{"key":"ref_95","first-page":"1504","article-title":"Lung Cancer","volume":"2009","author":"Neville","year":"2009","journal-title":"BMJ Clin. Evid."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"6640051","DOI":"10.1155\/2021\/6640051","article-title":"Lung Cancer Radiotherapy: Simulation and Analysis Based on a Multicomponent Mathematical Model","volume":"2021","author":"Hong","year":"2021","journal-title":"Comput. Math. Methods Med."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1111\/resp.13870","article-title":"Radiotherapy Treatment for Lung Cancer: Current Status and Future Directions","volume":"25","author":"Vinod","year":"2020","journal-title":"Respirology"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1093\/annonc\/mdz122","article-title":"Prognostic Value of Circulating Tumour Cells in Limited-Stage Small-Cell Lung Cancer: Analysis of the Concurrent Once-Daily versus Twice-Daily Radiotherapy (CONVERT) Randomised Controlled Trial","volume":"30","author":"Tay","year":"2019","journal-title":"Ann. Oncol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1016\/S1470-2045(17)30318-2","article-title":"Concurrent Once-Daily versus Twice-Daily Chemoradiotherapy in Patients with Limited-Stage Small-Cell Lung Cancer (CONVERT): An Open-Label, Phase 3, Randomised, Superiority Trial","volume":"18","author":"Snee","year":"2017","journal-title":"Lancet Oncol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"86615","DOI":"10.18632\/oncotarget.21255","article-title":"Prognostic Significance of Circulating Tumor Cells in Non-Small Cell Lung Cancer Patients Undergoing Chemotherapy","volume":"8","author":"Tong","year":"2017","journal-title":"Oncotarget"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"789","DOI":"10.2217\/fon.15.346","article-title":"Circulating Tumor Cell Counts\/Change for Outcome Prediction in Patients with Extensive-Stage Small-Cell Lung Cancer","volume":"12","author":"Cheng","year":"2016","journal-title":"Future Oncol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1038\/bjc.2017.137","article-title":"Second-Line Pazopanib in Patients with Relapsed and Refractory Small-Cell Lung Cancer: A Multicentre Phase II Study of the Hellenic Oncology Research Group","volume":"117","author":"Koinis","year":"2017","journal-title":"Br. J. Cancer"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1601","DOI":"10.3727\/096504017X14928634401178","article-title":"Circulating Tumor Cells Predict Prognosis Following Tyrosine Kinase Inhibitor Treatment in EGFR-Mutant Non-Small Cell Lung Cancer Patients","volume":"25","author":"Yang","year":"2017","journal-title":"Oncol. Res."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1186\/s40425-019-0649-2","article-title":"Circulating Tumor Cells in Advanced Non-Small Cell Lung Cancer Patients Are Associated with Worse Tumor Response to Checkpoint Inhibitors","volume":"7","author":"Tamminga","year":"2019","journal-title":"J. Immunother. Cancer"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"5910","DOI":"10.1002\/cam4.1832","article-title":"The Prognostic Significance of Circulating Tumor Cells in Head and Neck and Non-small-cell Lung Cancer","volume":"7","author":"Kulasinghe","year":"2018","journal-title":"Cancer Med."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1001\/jama.1946.02870380008004","article-title":"NITROGEN MUSTARD THERAPY: Use of Methyl-Bis(Beta-Chloroethyl)Amine Hydrochloride and Tris(Beta-Chloroethyl)Amine Hydrochloride for Hodgkin\u2019s Disease, Lymphosarcoma, Leukemia and Certain Allied and Miscellaneous Disorders","volume":"132","author":"Goodman","year":"1946","journal-title":"J. Am. Med. Assoc."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"115891","DOI":"10.1016\/j.biopha.2023.115891","article-title":"Advances and Challenges in the Treatment of Lung Cancer","volume":"169","author":"Li","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"2386","DOI":"10.1200\/JCO.2018.77.7672","article-title":"Randomized, Double-Blind, Phase II Study of Temozolomide in Combination With Either Veliparib or Placebo in Patients with Relapsed-Sensitive or Refractory Small-Cell Lung Cancer","volume":"36","author":"Pietanza","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"3371","DOI":"10.1039\/D4MD00384E","article-title":"Next-Generation EGFR Tyrosine Kinase Inhibitors to Overcome C797S Mutation in Non-Small Cell Lung Cancer (2019\u20132024)","volume":"15","author":"Das","year":"2024","journal-title":"RSC Med. Chem."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"107968","DOI":"10.1016\/j.lungcan.2024.107968","article-title":"Systematic Review and Network Meta-Analysis of Lorlatinib with Comparison to Other Anaplastic Lymphoma Kinase (ALK) Tyrosine Kinase Inhibitors (TKIs) as First-Line Treatment for ALK-Positive Advanced Non-Smallcell Lung Cancer (NSCLC)","volume":"197","author":"Ou","year":"2024","journal-title":"Lung Cancer"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1186\/s13045-020-00977-0","article-title":"Tyrosine Kinase Inhibitors for Solid Tumors in the Past 20 Years (2001\u20132020)","volume":"13","author":"Huang","year":"2020","journal-title":"J. Hematol. Oncol."},{"key":"ref_112","first-page":"1077","article-title":"Circulating Tumor Cells Predict Prognosis Following Second- Line AZD 9291 Treatment in EGFR-T790M Mutant Non-Small Cell Lung Cancer Patients","volume":"23","author":"Yang","year":"2018","journal-title":"J. BUON"},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Rui, R., Zhou, L., and He, S. (2023). Cancer Immunotherapies: Advances and Bottlenecks. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1212476"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"3782","DOI":"10.1158\/1078-0432.CCR-15-0855","article-title":"A Phase III Clinical Trial of the Epidermal Growth Factor Vaccine CIMAvax-EGF as Switch Maintenance Therapy in Advanced Non-Small Cell Lung Cancer Patients","volume":"22","author":"Rodriguez","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1016\/S1470-2045(11)70259-5","article-title":"Therapeutic Vaccination with TG4010 and First-Line Chemotherapy in Advanced Non-Small-Cell Lung Cancer: A Controlled Phase 2B Trial","volume":"12","author":"Quoix","year":"2011","journal-title":"Lancet Oncol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"2321","DOI":"10.1016\/j.ejca.2015.07.035","article-title":"A Phase III Study of Belagenpumatucel-L, an Allogeneic Tumour Cell Vaccine, as Maintenance Therapy for Non-Small Cell Lung Cancer","volume":"51","author":"Giaccone","year":"2015","journal-title":"Eur. J. Cancer"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"2923","DOI":"10.1002\/1878-0261.13094","article-title":"Clinical Potential of Circulating Free DNA and Circulating Tumour Cells in Patients with Metastatic Non-small-cell Lung Cancer Treated with Pembrolizumab","volume":"15","author":"Anido","year":"2021","journal-title":"Mol. Oncol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"67586","DOI":"10.18632\/oncotarget.11707","article-title":"Circulating Tumor Cells Predict Survival Benefit from Chemotherapy in Patients with Lung Cancer","volume":"7","author":"Wu","year":"2016","journal-title":"Oncotarget"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.trsl.2017.04.002","article-title":"Current Approaches for Avoiding the Limitations of Circulating Tumor Cells Detection Methods\u2014Implications for Diagnosis and Treatment of Patients with Solid Tumors","volume":"185","author":"Kowalik","year":"2017","journal-title":"Transl. Res."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"7021","DOI":"10.1002\/cam4.4236","article-title":"Prognostic Significance of Programmed Cell Death-Ligand 1 Expression on Circulating Tumor Cells in Various Cancers: A Systematic Review and Meta-Analysis","volume":"10","author":"Ouyang","year":"2021","journal-title":"Cancer Med."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1016\/j.jtho.2021.01.1617","article-title":"Prospective Multicenter Validation of the Detection of ALK Rearrangements of Circulating Tumor Cells for Noninvasive Longitudinal Management of Patients With Advanced NSCLC","volume":"16","author":"Chamorey","year":"2021","journal-title":"J. Thorac. Oncol."},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Ntzifa, A., Marras, T., Kallergi, G., Kotsakis, A., Georgoulias, V., and Lianidou, E. (2024). Comprehensive Liquid Biopsy Analysis for Monitoring NSCLC Patients under Second-Line Osimertinib Treatment. Front. Oncol., 14.","DOI":"10.3389\/fonc.2024.1435537"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/1\/384\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T05:22:12Z","timestamp":1767244932000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/1\/384"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,30]]},"references-count":122,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["ijms27010384"],"URL":"https:\/\/doi.org\/10.3390\/ijms27010384","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,30]]}}}