Espejo-Cruz, María LolaGonzález-Rubio, SandraZamora-Olaya, JavierAmado-Torres, VíctorAlejandre, RafaelSánchez-Frías, MarinaCiria, RubénDe la Mata, ManuelRodríguez-Perálvarez, ManuelFerrín, Gustavo2022-12-022022-12-022021-12-03Espejo-Cruz ML, González-Rubio S, Zamora-Olaya J, Amado-Torres V, Alejandre R, Sánchez-Frías M, et al. Circulating Tumor Cells in Hepatocellular Carcinoma: A Comprehensive Review and Critical Appraisal. Int J Mol Sci. 2021 Dec 3;22(23):13073http://hdl.handle.net/10668/4446Hepatocellular carcinoma (HCC) is the fifth most common neoplasm and a major cause of cancer-related death worldwide. There is no ideal biomarker allowing early diagnosis of HCC and tumor surveillance in patients receiving therapy. Liquid biopsy, and particularly circulating tumor cells (CTCs), have emerged as a useful tool for diagnosis and monitoring therapeutic responses in different tumors. In the present manuscript, we evaluate the current evidence supporting the quantitative and qualitative assessment of CTCs as potential biomarkers of HCC, as well as technical aspects related to isolation, identification, and classification of CTCs. Although the dynamic assessment of CTCs in patients with HCC may aid the decision-making process, there are still many uncertainties and technical caveats to be solved before this methodology has a true impact on clinical practice guidelines. More studies are needed to identify the optimal combination of surface markers, to increase the efficiency of ex-vivo expansion of CTCs, or even to target CTCs as a potential therapeutic strategy to prevent HCC recurrence after surgery or to hamper tumor progression and extrahepatic spreading.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/Hepatocellular carcinomaLiquid biopsyCirculating tumor cellsDynamic changesTherapeutic targetLiver cancerCarcinoma hepatocelularBiopsia líquidaCélulas neoplásicas circulantesNeoplasias hepáticasTerapéuticaMedical Subject Headings::Chemicals and Drugs::Biological Factors::Biological Markers::Biomarkers, PharmacologicalMedical Subject Headings::Diseases::Digestive System Diseases::Liver Diseases::Liver Neoplasms::Carcinoma, HepatocellularMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Diseases::Digestive System Diseases::Liver DiseasesMedical Subject Headings::Diseases::Neoplasms::Neoplastic Processes::Neoplasm Metastasis::Neoplastic Cells, CirculatingMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Early DiagnosisMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeuticsreview article34884878open access10.3390/ijms2223130731422-0067PMC8657934