{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T21:58:27Z","timestamp":1790891907722,"version":"4.1.0"},"reference-count":132,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,16]],"date-time":"2023-02-16T00:00:00Z","timestamp":1676505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health","award":["GR-2019-12369697"],"award-info":[{"award-number":["GR-2019-12369697"]}]},{"name":"Italian Ministry of Health","award":["RC ISG 2023"],"award-info":[{"award-number":["RC ISG 2023"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Precision medicine has driven a major change in the treatment of many forms of cancer. The discovery that each patient is different and each tumor mass has its own characteristics has shifted the focus of basic and clinical research to the singular individual. Liquid biopsy (LB), in this sense, presents new scenarios in personalized medicine through the study of molecules, factors, and tumor biomarkers in blood such as circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), exosomes and circulating tumor microRNAs (ct-miRNAs). Moreover, its easy application and complete absence of contraindications for the patient make this method applicable in a great many fields. Melanoma, given its highly heterogeneous characteristics, is a cancer form that could significantly benefit from the information linked to liquid biopsy, especially in the treatment management. In this review, we will focus our attention on the latest applications of liquid biopsy in metastatic melanoma and possible developments in the clinical setting.<\/jats:p>","DOI":"10.3390\/ijms24044014","type":"journal-article","created":{"date-parts":[[2023,2,17]],"date-time":"2023-02-17T01:59:24Z","timestamp":1676599164000},"page":"4014","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Metastatic Melanoma: Liquid Biopsy as a New Precision Medicine Approach"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8319-3861","authenticated-orcid":false,"given":"Elena","family":"Ricciardi","sequence":"first","affiliation":[{"name":"UOC Oncological Translational Research, IRCCS-Regina Elena National Cancer Institute, 00144 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6445-4509","authenticated-orcid":false,"given":"Elena","family":"Giordani","sequence":"additional","affiliation":[{"name":"UOC Oncological Translational Research, IRCCS-Regina Elena National Cancer Institute, 00144 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6829-981X","authenticated-orcid":false,"given":"Giovanna","family":"Ziccheddu","sequence":"additional","affiliation":[{"name":"UOC Oncological Translational Research, IRCCS-Regina Elena National Cancer Institute, 00144 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2796-0792","authenticated-orcid":false,"given":"Italia","family":"Falcone","sequence":"additional","affiliation":[{"name":"SAFU, Department of Research, Advanced Diagnostics, and Technological Innovation, IRCCS-Regina Elena National Cancer Institute, 00144 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizio","family":"Giacomini","sequence":"additional","affiliation":[{"name":"Clinical Trial Center, IRCSS-Regina Elena National Cancer Institute\/San Gallicano Dermatological Institute, 00144 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5281-4191","authenticated-orcid":false,"given":"Maurizio","family":"Fanciulli","sequence":"additional","affiliation":[{"name":"SAFU, Department of Research, Advanced Diagnostics, and Technological Innovation, IRCCS-Regina Elena National Cancer Institute, 00144 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelangelo","family":"Russillo","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology 1, IRCCS-Regina Elena National Cancer Institute, 00144 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianna","family":"Cerro","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Medicine, \u201cLa Sapienza\u201d, University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gennaro","family":"Ciliberto","sequence":"additional","affiliation":[{"name":"Scientific Direction, IRCCS-Regina Elena National Cancer Institute, 00144 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aldo","family":"Morrone","sequence":"additional","affiliation":[{"name":"Scientific Direction, San Gallicano Dermatological Institute IRCCS, 00144 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonino","family":"Guerrisi","sequence":"additional","affiliation":[{"name":"Radiology and Diagnostic Imaging Unit, Department of Clinical and Dermatological Research, San Gallicano Dermatological Institute IRCCS, 00144 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1098-7705","authenticated-orcid":false,"given":"Fabio","family":"Valenti","sequence":"additional","affiliation":[{"name":"UOC Oncological Translational Research, IRCCS-Regina Elena National Cancer Institute, 00144 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Falcone, I., Conciatori, F., Bazzichetto, C., Ferretti, G., Cognetti, F., Ciuffreda, L., and Milella, M. (2020). Tumor Microenvironment: Implications in Melanoma Resistance to Targeted Therapy and Immunotherapy. Cancers, 12.","DOI":"10.3390\/cancers12102870"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Valenti, F., Falcone, I., Ungania, S., Desiderio, F., Giacomini, P., Bazzichetto, C., Conciatori, F., Gallo, E., Cognetti, F., and Ciliberto, G. (2021). Precision Medicine and Melanoma: Multi-Omics Approaches to Monitoring the Immunotherapy Response. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22083837"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Perakis, S., and Speicher, M.R. (2017). Emerging concepts in liquid biopsies. BMC Med., 15.","DOI":"10.1186\/s12916-017-0840-6"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"704607","DOI":"10.3389\/fonc.2021.704607","article-title":"Exploring CT Texture Parameters as Predictive and Response Imaging Biomarkers of Survival in Patients with Metastatic Melanoma Treated With PD-1 Inhibitor Nivolumab: A Pilot Study Using a Delta-Radiomics Approach","volume":"11","author":"Guerrisi","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1200\/OP.21.00686","article-title":"Managing Metastatic Melanoma in 2022: A Clinical Review","volume":"18","author":"Switzer","year":"2022","journal-title":"JCO Oncol. Pract."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.molonc.2015.12.008","article-title":"Liquid biopsy utility for the surveillance of cutaneous malignant melanoma patients","volume":"10","author":"Huang","year":"2015","journal-title":"Mol. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.bbcan.2019.02.002","article-title":"Many ways to resistance: How melanoma cells evade targeted therapies","volume":"1871","author":"Kozar","year":"2019","journal-title":"Biochim. Biophys. Acta Rev. Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"645069","DOI":"10.3389\/fonc.2021.645069","article-title":"The Promise of Liquid Biopsy to Predict Response to Immunotherapy in Metastatic Melanoma","volume":"11","author":"Fattore","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1002\/onco.13926","article-title":"Liquid Biopsy and Radiological Response Predict Outcomes Following Discontinuation of Targeted Therapy in Patients with BRAF Mutated Melanoma","volume":"26","author":"Randon","year":"2021","journal-title":"Oncologist"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.canlet.2017.06.030","article-title":"Circulating tumour DNA (ctDNA) as a liquid biopsy for melanoma","volume":"404","author":"Calapre","year":"2017","journal-title":"Cancer Lett."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"adv00136","DOI":"10.2340\/00015555-3491","article-title":"Melanoma Epidemiology and Sun Exposure","volume":"100","author":"Raimondi","year":"2020","journal-title":"Acta Derm. Venereol."},{"key":"ref_12","first-page":"23","article-title":"The role of tumor microenvironment in development and progression of malignant melanomas\u2014A systematic review","volume":"59","author":"Gurzu","year":"2018","journal-title":"Rom. J. Morphol. Embryol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Steininger, J., Gellrich, F., Schulz, A., Westphal, D., Beissert, S., and Meier, F. (2021). Systemic Therapy of Metastatic Melanoma: On the Road to Cure. Cancers, 13.","DOI":"10.3390\/cancers13061430"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3947","DOI":"10.1200\/JCO.20.00198","article-title":"Systemic Therapy for Melanoma: ASCO Guideline","volume":"38","author":"Seth","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.1016\/j.annonc.2020.07.004","article-title":"ESMO consensus conference recommendations on the management of metastatic melanoma: Under the auspices of the ESMO Guidelines Committee","volume":"31","author":"Keilholz","year":"2020","journal-title":"Ann. Oncol."},{"key":"ref_16","unstructured":"Edge, S., Byrd, D., Compton, C., Fritz, A., Greene, F., and Trotti, A. (2009). AJCC Cancer Staging Manual, Springer. [7th ed.]."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Ward, W.H., Lambreton, F., Goel, N., Yu, J.Q., and Farma, J.M. Clinical Presentation and Staging of Melanoma; Brisbane, QL, Australia, 2017; pp. 79\u201389.","DOI":"10.15586\/codon.cutaneousmelanoma.2017.ch6"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1080\/14737140.2018.1489246","article-title":"The eighth edition American Joint Committee on Cancer (AJCC) melanoma staging system: Implications for melanoma treatment and care","volume":"18","author":"Keung","year":"2018","journal-title":"Expert Rev. Anticancer Ther."},{"key":"ref_19","first-page":"1899","article-title":"A meta-analysis of transcriptome datasets characterizes malignant transformation from melanocytes and nevi to melanoma","volume":"16","author":"Moreno","year":"2018","journal-title":"Oncol. Lett."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1111\/pcmr.12572","article-title":"Evaluation of tubulin\u03b2-3 as a novel senescence-associated gene in melanocytic malignant transformation","volume":"30","author":"Orfanidis","year":"2017","journal-title":"Pigment. Cell Melanoma Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1038\/ng1148","article-title":"Melanoma mouse model implicates metabotropic glutamate signaling in melanocytic neoplasia","volume":"34","author":"Pollock","year":"2003","journal-title":"Nat. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1926","DOI":"10.1056\/NEJMoa1502583","article-title":"The Genetic Evolution of Melanoma from Precursor Lesions","volume":"373","author":"Shain","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_23","first-page":"1071","article-title":"Cutaneous melanoma: From pathogenesis to therapy (Review)","volume":"52","author":"Leonardi","year":"2018","journal-title":"Int. J. Oncol."},{"key":"ref_24","first-page":"1997","article-title":"ERK\/MAPK signalling pathway and tumorigenesis","volume":"19","author":"Guo","year":"2020","journal-title":"Exp. Ther. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"D941","DOI":"10.1093\/nar\/gky1015","article-title":"COSMIC: The Catalogue of Somatic Mutations in Cancer","volume":"47","author":"Tate","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Braicu, C., Buse, M., Busuioc, C., Drula, R., Gulei, D., Raduly, L., Rusu, A., Irimie, A., Atanasov, A.G., and Slaby, O. (2019). A Comprehensive Review on MAPK: A Promising Therapeutic Target in Cancer. Cancers, 11.","DOI":"10.3390\/cancers11101618"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1038\/s41389-018-0081-3","article-title":"Oncogenic PI3K\/AKT promotes the step-wise evolution of combination BRAF\/MEK inhibitor resistance in melanoma","volume":"7","author":"Irvine","year":"2018","journal-title":"Oncogenesis"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Bazzichetto, C., Conciatori, F., Pallocca, M., Falcone, I., Fanciulli, M., Cognetti, F., Milella, M., and Ciuffreda, L. (2019). PTEN as a Prognostic\/Predictive Biomarker in Cancer: An Unfulfilled Promise?. Cancers, 11.","DOI":"10.3390\/cancers11040435"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1136\/jclinpath-2021-208008","article-title":"PTEN as a target in melanoma","volume":"75","author":"Ince","year":"2022","journal-title":"J. Clin. Pathol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/s10555-016-9613-5","article-title":"Genetic progression of malignant melanoma","volume":"35","author":"Vizkeleti","year":"2016","journal-title":"Cancer Metastasis Rev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1056\/NEJMoa1113205","article-title":"Intratumor heterogeneity and branched evolution revealed by multiregion sequencing","volume":"366","author":"Gerlinger","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_32","first-page":"33","article-title":"Detection of low frequency FGFR3 mutations in the urine of bladder cancer patients using next-generation deep sequencing","volume":"4","author":"Millholland","year":"2012","journal-title":"Res. Rep. Urol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"293ra104","DOI":"10.1126\/scitranslmed.aaa8507","article-title":"Detection of somatic mutations and HPV in the saliva and plasma of patients with head and neck squamous cell carcinomas","volume":"7","author":"Wang","year":"2015","journal-title":"Sci. Transl. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/s11910-018-0820-z","article-title":"Liquid Biopsy in Primary Brain Tumors: Looking for Stardust!","volume":"18","author":"Fontanilles","year":"2018","journal-title":"Curr. Neurol. Neursci. Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1159\/000499337","article-title":"Liquid Biopsy: General Concepts","volume":"63","author":"Poulet","year":"2019","journal-title":"Acta Cytol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1758835918794630","DOI":"10.1177\/1758835918794630","article-title":"Liquid biopsy of cancer: A multimodal diagnostic tool in clinical oncology","volume":"10","author":"Palmirotta","year":"2018","journal-title":"Ther. Adv. Med Oncol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1038\/jid.2013.34","article-title":"Circulating Melanoma Cells as a Predictive Biomarker","volume":"133","author":"Karakousis","year":"2013","journal-title":"J. Investig. Dermatol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.jamcollsurg.2018.04.026","article-title":"Circulating Tumor Cells in Stage IV Melanoma Patients","volume":"227","author":"Hall","year":"2018","journal-title":"J. Am. Coll. Surg."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1886","DOI":"10.1158\/1078-0432.CCR-19-2670","article-title":"Circulating Tumor Cells and Early Relapse in Node-positive Melanoma","volume":"26","author":"Lucci","year":"2020","journal-title":"Clin. Cancer Res."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Kiniwa, Y., Nakamura, K., Mikoshiba, A., Ashida, A., Akiyama, Y., Morimoto, A., and Okuyama, R. (2021). Usefulness of monitoring circulating tumor cells as a therapeutic biomarker in melanoma with BRAF mutation. BMC Cancer, 21.","DOI":"10.1186\/s12885-021-08016-y"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e520","DOI":"10.1634\/theoncologist.2019-0557","article-title":"PD-L1 Expression on Circulating Tumor Cells May Be Predictive of Response to Pembrolizumab in Advanced Melanoma: Results from a Pilot Study","volume":"25","author":"Khattak","year":"2019","journal-title":"Oncologist"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2467","DOI":"10.1073\/pnas.1719264115","article-title":"Molecular signatures of circulating melanoma cells for monitoring early response to immune checkpoint therapy","volume":"115","author":"Hong","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"4064","DOI":"10.1158\/1078-0432.CCR-19-3926","article-title":"Longitudinal Monitoring of ctDNA in Patients with Melanoma and Brain Metastases Treated with Immune Checkpoint Inhibitors","volume":"26","author":"Lee","year":"2020","journal-title":"Clin. Cancer Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-020-75792-1","article-title":"Circulating tumor DNA (ctDNA) detection is associated with shorter progression-free survival in advanced melanoma patients","volume":"10","author":"Marczynski","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"5926","DOI":"10.1158\/1078-0432.CCR-20-2251","article-title":"Circulating Tumor DNA Predicts Outcome from First-, but not Second-line Treatment and Identifies Melanoma Patients Who May Benefit from Combination Immunotherapy","volume":"26","author":"Marsavela","year":"2020","journal-title":"Clin. Cancer Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1038\/s41416-021-01507-6","article-title":"Detection of clinical progression through plasma ctDNA in metastatic melanoma patients: A comparison to radiological progression","volume":"126","author":"Marsavela","year":"2021","journal-title":"Br. J. Cancer"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1038\/jid.2012.493","article-title":"Methylated Tissue Factor Pathway Inhibitor 2 (TFPI2) DNA in Serum Is a Biomarker of Metastatic Melanoma","volume":"133","author":"Nigro","year":"2013","journal-title":"J. Investig. Dermatol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/s41598-019-56542-4","article-title":"Melanoma cell-derived exosomes in plasma of melanoma patients suppress functions of immune effector cells","volume":"10","author":"Sharma","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1710899","DOI":"10.1080\/20013078.2019.1710899","article-title":"Tracking the evolution of circulating exosomal-PD-L1 to monitor melanoma patients","volume":"9","author":"Cordonnier","year":"2020","journal-title":"J. Extracell. Vesicles"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.cca.2015.12.031","article-title":"Circulating melanoma exosomes as diagnostic and prognosis biomarkers","volume":"454","author":"Alegre","year":"2016","journal-title":"Clin. Chim. Acta"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1186\/s12967-022-03668-1","article-title":"A novel microRNA signature for the detection of melanoma by liquid biopsy","volume":"20","author":"Sabato","year":"2022","journal-title":"J. Transl. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"7420","DOI":"10.7150\/thno.77761","article-title":"Identification of a miRNA-based non-invasive predictive biomarker of response to target therapy in BRAF-mutant melanoma","volume":"12","author":"Ruggiero","year":"2022","journal-title":"Theranostics"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1038\/bjc.2017.477","article-title":"Development and validation of a plasma-based melanoma biomarker suitable for clinical use","volume":"118","author":"Lincoln","year":"2018","journal-title":"Br. J. Cancer"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/j.ebiom.2015.05.011","article-title":"The Prognostic and Predictive Value of Melanoma-related MicroRNAs Using Tissue and Serum: A MicroRNA Expression Analysis","volume":"2","author":"Stark","year":"2015","journal-title":"Ebiomedicine"},{"key":"ref_55","first-page":"e126","article-title":"Circulating mi RNA expression analysis reveals new potential biomarkers for human cutaneous melanoma staging","volume":"34","author":"Navarro","year":"2019","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/s12967-020-02235-w","article-title":"Poor clinical outcome in metastatic melanoma is associated with a microRNA-modulated immunosuppressive tumor microenvironment","volume":"18","author":"Jorge","year":"2020","journal-title":"J. Transl. Med."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Bustos, M., Gross, R., Rahimzadeh, N., Cole, H., Tran, L., Tran, K., Takeshima, L., Stern, S., O\u2019Day, S., and Hoon, D. (2020). A Pilot Study Comparing the Efficacy of Lactate Dehydrogenase Levels Versus Circulating Cell-Free microRNAs in Monitoring Responses to Checkpoint Inhibitor Immunotherapy in Metastatic Melanoma Patients. Cancers, 12.","DOI":"10.3390\/cancers12113361"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/j.molmed.2010.07.001","article-title":"Circulating tumour cells in cancer patients: Challenges and perspectives","volume":"16","author":"Pantel","year":"2010","journal-title":"Trends Mol. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1016\/j.tips.2022.02.005","article-title":"Circulating tumor cells in precision medicine: Challenges and opportunities","volume":"43","author":"Rupp","year":"2022","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1039\/C7LC00955K","article-title":"Machine learning to detect signatures of disease in liquid biopsies\u2014A user\u2019s guide","volume":"18","author":"Ko","year":"2017","journal-title":"Lab Chip"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.21873\/invivo.11571","article-title":"Circulating Tumor Cells in Diagnosis and Treatment of Lung Cancer","volume":"33","author":"Maly","year":"2019","journal-title":"Vivo"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2349","DOI":"10.1038\/jid.2010.215","article-title":"Circulating Tumor Cells and Melanoma Progression","volume":"130","author":"Xu","year":"2010","journal-title":"J. Investig. Dermatol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1002\/hep.31165","article-title":"Detection of circulating tumor cells and their implications as a novel biomarker for diagnosis, prognostication, and therapeutic monitoring in hepatocellular carcinoma","volume":"73","author":"Ahn","year":"2020","journal-title":"Hepatology"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"HEP10","DOI":"10.2217\/hep-2018-0005","article-title":"Molecular heterogeneity in hepatocellular carcinoma","volume":"5","author":"Zhu","year":"2018","journal-title":"Hepatic Oncol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"6302","DOI":"10.1158\/1078-0432.CCR-08-0872","article-title":"Circulating Tumor Cells Predict Survival Benefit from Treatment in Metastatic Castration-Resistant Prostate Cancer","volume":"14","author":"Scher","year":"2008","journal-title":"Clin. Cancer Res."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Francescangeli, F., Magri, V., De Angelis, M.L., De Renzi, G., Gandini, O., Zeuner, A., Gazzaniga, P., and Nicolazzo, C. (2021). Sequential Isolation and Characterization of Single CTCs and Large CTC Clusters in Metastatic Colorectal Cancer Patients. Cancers, 13.","DOI":"10.3390\/cancers13246362"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"62754","DOI":"10.18632\/oncotarget.11191","article-title":"Technical challenges in the isolation and analysis of circulating tumor cells","volume":"7","author":"Verdone","year":"2016","journal-title":"Oncotarget"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1586\/14737159.2015.1091729","article-title":"Liquid biopsy in cancer patients: Advances in capturing viable CTCs for functional studies using the EPISPOT assay","volume":"15","author":"Pantel","year":"2015","journal-title":"Expert Rev. Mol. Diagn."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Shoji, Y., Bustos, M.A., Gross, R., and Hoon, D.S.B. (2022). Recent Developments of Circulating Tumor Cell Analysis for Monitoring Cutaneous Melanoma Patients. Cancers, 14.","DOI":"10.3390\/cancers14040859"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"95","DOI":"10.21147\/j.issn.1000-9604.2022.02.04","article-title":"Establishment of an optimized CTC detection model consisting of EpCAM, MUC1 and WT1 in epithelial ovarian cancer and its correlation with clinical characteristics","volume":"34","author":"Wang","year":"2022","journal-title":"Chin. J. Cancer Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.humpath.2003.08.026","article-title":"Frequent EpCam protein expression in human carcinomas","volume":"35","author":"Went","year":"2004","journal-title":"Hum. Pathol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1007\/s10555-020-09898-3","article-title":"Expression and function of epithelial cell adhesion molecule EpCAM: Where are we after 40 years?","volume":"39","author":"Gires","year":"2020","journal-title":"Cancer Metastasis Rev."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/1475-2867-6-26","article-title":"Expression of EpCAM in uveal melanoma","volume":"6","author":"Odashiro","year":"2006","journal-title":"Cancer Cell Int."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Cayrefourcq, L., De Roeck, A., Garcia, C., Stoebner, P.-E., Fichel, F., Garima, F., Perriard, F., Daures, J.-P., Meunier, L., and Alix-Panabi\u00e8res, C. (2019). S100-EPISPOT: A New Tool to Detect Viable Circulating Melanoma Cells. Cells, 8.","DOI":"10.3390\/cells8070755"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1126\/scitranslmed.3007094","article-title":"Detection of circulating tumor DNA in early- and late-stage human malignancies","volume":"6","author":"Bettegowda","year":"2014","journal-title":"Sci. Transl. Med."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1649","DOI":"10.1111\/brv.12413","article-title":"The diverse origins of circulating cell-free DNA in the human body: A critical re-evaluation of the literature","volume":"93","author":"Aucamp","year":"2018","journal-title":"Biol. Rev."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Lin, C., Liu, X., Zheng, B., Ke, R., and Tzeng, C.-M. (2021). Liquid Biopsy, ctDNA Diagnosis through NGS. Life, 11.","DOI":"10.3390\/life11090890"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1080\/15384047.2019.1598759","article-title":"Life and death of circulating cell-free DNA","volume":"20","author":"Kustanovich","year":"2019","journal-title":"Cancer Biol. Ther."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1016\/j.omto.2021.06.016","article-title":"Systematic review of the immunological landscape of Wilms tumors","volume":"22","author":"Palmisani","year":"2021","journal-title":"Mol. Ther. Oncolytics"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1182\/hematology.2019000013","article-title":"Prognostication with circulating tumor DNA: Is it ready for prime time?","volume":"2019","author":"Kurtz","year":"2019","journal-title":"Hematology"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11912-017-0564-y","article-title":"The Emerging Role of \u201cLiquid Biopsies,\u201d Circulating Tumor Cells, and Circulating Cell-Free Tumor DNA in Lung Cancer Diagnosis and Identification of Resistance Mutations","volume":"19","author":"Esposito","year":"2017","journal-title":"Curr. Oncol. Rep."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Morandi, L., De Biase, D., Visani, M., Cesari, V., De Maglio, G., Pizzolitto, S., Pession, A., and Tallini, G. (2012). Allele Specific Locked Nucleic Acid Quantitative PCR (ASLNAqPCR): An Accurate and Cost-Effective Assay to Diagnose and Quantify KRAS and BRAF Mutation. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0036084"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1586\/14737159.2013.845088","article-title":"Diagnostic and prognostic value of circulating tumor-related DNA in cancer patients","volume":"13","author":"Marzese","year":"2013","journal-title":"Expert Rev. Mol. Diagn."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.gpb.2016.12.004","article-title":"Circulating Tumor DNA as Biomarkers for Cancer Detection","volume":"15","author":"Han","year":"2017","journal-title":"Genom. Proteom. Bioinform."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.jmoldx.2016.09.009","article-title":"A Comparison of Cell-Free DNA Isolation Kits","volume":"19","author":"Sorber","year":"2016","journal-title":"J. Mol. Diagn."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1158\/2159-8290.CD-20-1311","article-title":"Liquid Biopsy: From Discovery to Clinical Application","volume":"11","author":"Pantel","year":"2021","journal-title":"Cancer Discov."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2068","DOI":"10.1158\/1078-0432.CCR-06-2120","article-title":"Utility of Circulating B-RAF DNA Mutation in Serum for Monitoring Melanoma Patients Receiving Biochemotherapy","volume":"13","author":"Shinozaki","year":"2007","journal-title":"Clin. Cancer Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.jdermsci.2021.04.006","article-title":"Liquid biopsy-based analysis by ddPCR and CAPP-Seq in melanoma patients","volume":"102","author":"Kaneko","year":"2021","journal-title":"J. Dermatol. Sci."},{"key":"ref_89","first-page":"646","article-title":"Free DNA in the serum of cancer patients and the effect of therapy","volume":"37","author":"Leon","year":"1977","journal-title":"Cancer Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"42008","DOI":"10.18632\/oncotarget.5788","article-title":"Circulating tumor DNA to monitor treatment response and detect acquired resistance in patients with metastatic melanoma","volume":"6","author":"Gray","year":"2015","journal-title":"Oncotarget"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Tellez-Gabriel, M., Knutsen, E., and Perander, M. (2020). Current Status of Circulating Tumor Cells, Circulating Tumor DNA, and Exosomes in Breast Cancer Liquid Biopsies. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21249457"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"100516","DOI":"10.1016\/j.currproblcancer.2019.100516","article-title":"Circulating tumor DNA\/circulating tumor cells and the applicability in different causes induced hepatocellular carcinoma","volume":"44","author":"Li","year":"2019","journal-title":"Curr. Probl. Cancer"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Trejo-Becerril, C., P\u00e9rez-C\u00e1rdenas, E., Taja-Chayeb, L., Anker, P., Herrera-Goepfert, R., Medina-Vel\u00e1zquez, L.A., Hidalgo-Miranda, A., P\u00e9rez-Montiel, D., Ch\u00e1vez-Blanco, A., and Cruz-Vel\u00e1zquez, J. (2012). Cancer Progression Mediated by Horizontal Gene Transfer in an In Vivo Model. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0052754"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1111\/pcmr.12682","article-title":"Survival and prognostic factors for patients with melanoma brain metastases in the era of modern systemic therapy","volume":"31","author":"Tio","year":"2018","journal-title":"Pigment. Cell Melanoma Res."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1146\/annurev-biochem-013118-111902","article-title":"Exosomes","volume":"88","author":"Pegtel","year":"2019","journal-title":"Annu. Rev. Biochem."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"4136","DOI":"10.1038\/s41467-019-11534-w","article-title":"Exosome reporter mice reveal the involvement of exosomes in mediating neuron to astroglia communication in the CNS","volume":"10","author":"Men","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1977","DOI":"10.1182\/blood-2008-08-174094","article-title":"Activated T cells recruit exosomes secreted by dendritic cells via LFA-1","volume":"113","author":"Nolte","year":"2009","journal-title":"Blood"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1038\/sj.leu.2404132","article-title":"Embryonic stem cell-derived microvesicles reprogram hematopoietic progenitors: Evidence for horizontal transfer of mRNA and protein delivery","volume":"20","author":"Ratajczak","year":"2006","journal-title":"Leukemia"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"8019","DOI":"10.2147\/IJN.S272378","article-title":"Cancer-Derived Exosomes: Their Role in Cancer Biology and Biomarker Development","volume":"ume 15","author":"Kok","year":"2020","journal-title":"Int. J. Nanomed."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Zhou, Y., Zhang, Y., Gong, H., Luo, S., and Cui, Y. (2021). The Role of Exosomes and Their Applications in Cancer. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222212204"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1016\/j.ccell.2016.10.009","article-title":"Extracellular Vesicles in Cancer: Cell-to-Cell Mediators of Metastasis","volume":"30","author":"Becker","year":"2016","journal-title":"Cancer Cell"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1007\/978-1-0716-1205-7_23","article-title":"Immunoaffinity-Based Isolation of Melanoma Cell-Derived and T Cell-Derived Exosomes from Plasma of Melanoma Patients","volume":"2265","author":"Mondal","year":"2021","journal-title":"Melanoma Methods Protoc."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1186\/s12943-019-1074-3","article-title":"The role of exosomal PD-L1 in tumor progression and immunotherapy","volume":"18","author":"Xie","year":"2019","journal-title":"Mol. Cancer"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1002\/prca.201400114","article-title":"Exosomes in bodily fluids are a highly stable resource of disease biomarkers","volume":"9","author":"Boukouris","year":"2015","journal-title":"Proteom. Clin. Appl."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1038\/s41586-018-0392-8","article-title":"Exosomal PD-L1 contributes to immunosuppression and is associated with anti-PD-1 response","volume":"560","author":"Chen","year":"2018","journal-title":"Nature"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1136\/gutjnl-2020-323014","article-title":"Exosome-delivered CD44v6\/C1QBP complex drives pancreatic cancer liver metastasis by promoting fibrotic liver microenvironment","volume":"71","author":"Xie","year":"2021","journal-title":"Gut"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"3085","DOI":"10.1080\/15384101.2019.1669380","article-title":"Melanoma-derived exosomes induce reprogramming fibroblasts into cancer-associated fibroblasts via Gm26809 delivery","volume":"18","author":"Hu","year":"2019","journal-title":"Cell Cycle"},{"key":"ref_108","first-page":"153","article-title":"Exosomes produced by melanoma cells significantly influence the biological properties of normal and cancer-associated fibroblasts","volume":"157","author":"Vokurka","year":"2021","journal-title":"Histochem."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1016\/j.trecan.2020.03.002","article-title":"Exosomal PD-L1: Roles in Tumor Progression and Immunotherapy","volume":"6","author":"Morrissey","year":"2020","journal-title":"Trends Cancer"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.imlet.2012.07.006","article-title":"Melanoma cell-derived exosomes alter macrophage and dendritic cell functions in vitro","volume":"148","author":"Marton","year":"2012","journal-title":"Immunol. Lett."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1172\/JCI87316","article-title":"Extracellular vesicles: Masters of intercellular communication and potential clinical interventions","volume":"126","author":"Pitt","year":"2016","journal-title":"J. Clin. Investig."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1016\/j.jaci.2017.08.034","article-title":"MicroRNA","volume":"141","author":"Lu","year":"2018","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"626","DOI":"10.3389\/fgene.2019.00626","article-title":"Circulating MicroRNAs in Cancer: Potential and Challenge","volume":"10","author":"Cui","year":"2019","journal-title":"Front. Genet."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"873728","DOI":"10.3389\/fmed.2022.873728","article-title":"Current Trends in Circulating Biomarkers for Melanoma Detection","volume":"9","author":"Huang","year":"2022","journal-title":"Front. Med."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.clinbiochem.2013.02.015","article-title":"Pre-analytical variables in miRNA analysis","volume":"46","author":"Becker","year":"2013","journal-title":"Clin. Biochem."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"100825","DOI":"10.1016\/j.mam.2019.10.002","article-title":"Circulating miRNA analysis for cancer diagnostics and therapy","volume":"72","author":"Valihrach","year":"2019","journal-title":"Mol. Asp. Med."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1614","DOI":"10.1038\/bjc.2014.451","article-title":"Plasma microRNA profiles: Identification of miR-25 as a novel diagnostic and monitoring biomarker in oesophageal squamous cell carcinoma","volume":"111","author":"Komatsu","year":"2014","journal-title":"Br. J. Cancer"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1038\/bjc.2015.366","article-title":"Plasma microRNA profiles: Identification of miR-744 as a novel diagnostic and prognostic biomarker in pancreatic cancer","volume":"113","author":"Miyamae","year":"2015","journal-title":"Br. J. Cancer"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"10317","DOI":"10.18632\/oncotarget.23126","article-title":"Circulating microRNA-196a is an early gastric cancer biomarker","volume":"9","author":"Chen","year":"2017","journal-title":"Oncotarget"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"62034","DOI":"10.18632\/oncotarget.11500","article-title":"Plasma microRNA profiles: Identification of miR-23a as a novel biomarker for chemoresistance in esophageal squamous cell carcinoma","volume":"7","author":"Komatsu","year":"2016","journal-title":"Oncotarget"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"165847","DOI":"10.1016\/j.bbadis.2020.165847","article-title":"Identifying circulating miRNA biomarkers for early diagnosis and monitoring of lung cancer","volume":"1866","author":"Zhang","year":"2020","journal-title":"Biochim. Biophys. Acta (BBA) Mol. Basis Dis."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"2628","DOI":"10.7150\/ijbs.47203","article-title":"miRNA-based biomarkers, therapies, and resistance in Cancer","volume":"16","author":"He","year":"2020","journal-title":"Int. J. Biol. Sci."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1007\/s11060-019-03256-2","article-title":"Clinical impact of circulating oncogenic MiRNA-221 and MiRNA-222 in glioblastoma multiform","volume":"144","author":"Swellam","year":"2019","journal-title":"J. Neuro-Oncol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"6513","DOI":"10.18632\/oncotarget.14311","article-title":"A six-microRNA panel in plasma was identified as a potential biomarker for lung adenocarcinoma diagnosis","volume":"8","author":"Zhou","year":"2016","journal-title":"Oncotarget"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.gene.2016.01.042","article-title":"Study of microRNAs-21\/221 as potential breast cancer biomarkers in Egyptian women","volume":"590","author":"Motawi","year":"2016","journal-title":"Gene"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1111\/cen.13972","article-title":"New molecular biomarkers in differentiated thyroid carcinoma: Impact of miR-146, miR-221 and miR-222 levels in the evolution of the disease","volume":"91","author":"Pareja","year":"2019","journal-title":"Clin. Endocrinol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"3953","DOI":"10.1158\/1078-0432.CCR-16-1464","article-title":"In Hepatocellular Carcinoma miR-221 Modulates Sorafenib Resistance through Inhibition of Caspase-3\u2013Mediated Apoptosis","volume":"23","author":"Fornari","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.ccell.2016.07.007","article-title":"RETRACTED: Downregulation of p53-inducible microRNAs 192, 194, and 215 Impairs the p53\/MDM2 Autoregulatory Loop in Multiple Myeloma Development","volume":"30","author":"Pichiorri","year":"2016","journal-title":"Cancer Cell"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"608987","DOI":"10.3389\/fonc.2021.608987","article-title":"MicroRNA Signature in Melanoma: Biomarkers and Therapeutic Targets","volume":"11","author":"Gholipour","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.semcancer.2019.12.008","article-title":"Natural products targeting the PI3K-Akt-mTOR signaling pathway in cancer: A novel therapeutic strategy","volume":"Volume 80","author":"Tewari","year":"2019","journal-title":"Seminars in Cancer Biology"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.gendis.2020.06.005","article-title":"The Nuclear Factor Kappa B (NF-kB) signaling in cancer development and immune diseases","volume":"8","author":"Zinatizadeh","year":"2020","journal-title":"Genes Dis."},{"key":"ref_132","doi-asserted-by":"crossref","unstructured":"Mumford, S.L., Towler, B.P., Pashler, A.L., Gilleard, O., Martin, Y., and Newbury, S.F. (2018). Circulating MicroRNA Biomarkers in Melanoma: Tools and Challenges in Personalised Medicine. 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