{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,25]],"date-time":"2026-01-25T03:27:08Z","timestamp":1769311628406,"version":"3.49.0"},"reference-count":100,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,4,7]],"date-time":"2021-04-07T00:00:00Z","timestamp":1617753600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["NORTE-01-0247-FEDER-033533"],"award-info":[{"award-number":["NORTE-01-0247-FEDER-033533"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia - FCT","award":["UID\/MULTI\/04046\/2021 UID\/MULTI\/04046\/2021"],"award-info":[{"award-number":["UID\/MULTI\/04046\/2021 UID\/MULTI\/04046\/2021"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Non-small-cell lung cancer (NSCLC) is a major cause of death worldwide. Alterations in such genes as EGFR and ALK are considered important biomarkers in NSCLC due to the existence of targeted therapies with specific tyrosine kinase inhibitors (TKIs). However, specific resistance-related mutations can occur during TKI treatment, which often result in therapy inefficacy. Liquid biopsies arise as a reliable tool for the early detection of these types of alterations, allowing a non-invasive follow-up of the patients. Furthermore, they can be essential for cancer screening, initial diagnosis and to check surgery success. Despite the great advantages of liquid biopsies in NSCLC and the high input that next-generation sequencing (NGS) approaches can provide in this field, its use in oncology is still limited. With improvement of assay sensitivity and the establishment of clinical guidelines for liquid biopsy analysis, it is expected that they will be used in routine procedures. This review focuses on the usefulness of liquid biopsies of NSCLC patients as a means to detect alterations in EGFR and ALK genes and in disease management, highlighting the impact of NGS methods.<\/jats:p>","DOI":"10.3390\/ijms22083815","type":"journal-article","created":{"date-parts":[[2021,4,7]],"date-time":"2021-04-07T11:31:59Z","timestamp":1617795119000},"page":"3815","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Future Perspectives in Detecting EGFR and ALK Gene Alterations in Liquid Biopsies of Patients with NSCLC"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7094-4969","authenticated-orcid":false,"given":"Daniela","family":"Ferreira","sequence":"first","affiliation":[{"name":"Biosystems and Integrative Sciences Institute (BioISI), Faculty of Sciences,  University of Lisboa, 1749-016 Lisbon, Portugal"}]},{"given":"Juliana","family":"Miranda","sequence":"additional","affiliation":[{"name":"Biosystems and Integrative Sciences Institute (BioISI), Faculty of Sciences,  University of Lisboa, 1749-016 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8229-0117","authenticated-orcid":false,"given":"Paula","family":"Martins-Lopes","sequence":"additional","affiliation":[{"name":"Biosystems and Integrative Sciences Institute (BioISI), Faculty of Sciences,  University of Lisboa, 1749-016 Lisbon, Portugal"},{"name":"Department of Genetics and Biotechnology (DGB), University of Tr\u00e1s-os-Montes e Alto Douro (UTAD), 5000-801 Vila Real, Portugal"}]},{"given":"Filomena","family":"Adega","sequence":"additional","affiliation":[{"name":"Biosystems and Integrative Sciences Institute (BioISI), Faculty of Sciences,  University of Lisboa, 1749-016 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5970-7428","authenticated-orcid":false,"given":"Raquel","family":"Chaves","sequence":"additional","affiliation":[{"name":"Biosystems and Integrative Sciences Institute (BioISI), Faculty of Sciences,  University of Lisboa, 1749-016 Lisbon, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"eaay1984","DOI":"10.1126\/scitranslmed.aay1984","article-title":"Applications of liquid biopsies for cancer","volume":"11","author":"Mattox","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"346ra392","DOI":"10.1126\/scitranslmed.aaf6219","article-title":"Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer","volume":"8","author":"Tie","year":"2016","journal-title":"Sci. Transl. Med."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Palmirotta, R., Lovero, D., Cafforio, P., Felici, C., Mannavola, F., Pelle, E., Quaresmini, D., Tucci, M., and Silvestris, F. (2018). Liquid biopsy of cancer: A multimodal diagnostic tool in clinical oncology. Ther. Adv. Med. Oncol., 10.","DOI":"10.1177\/1758835918794630"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"S113","DOI":"10.21037\/jtd.2018.12.18","article-title":"Circulating free tumor DNA in non-small cell lung cancer (NSCLC): Clinical application and future perspectives","volume":"11","author":"Herbreteau","year":"2019","journal-title":"J. Thorac. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"204","DOI":"10.4132\/jptm.2020.02.27","article-title":"Current status and future perspectives of liquid biopsy in non-small cell lung cancer","volume":"54","author":"Chang","year":"2020","journal-title":"J. Pathol. Transl. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1177\/107327480601300207","article-title":"Epidermal growth factor receptor-targeted agents for lung cancer","volume":"13","author":"Martin","year":"2006","journal-title":"Cancer Control"},{"key":"ref_7","first-page":"48","article-title":"Epidermal growth factor receptor (EGFR) in lung cancer: An overview and update","volume":"2","author":"Bethune","year":"2010","journal-title":"J. Thorac. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-019-39965-x","article-title":"Mutational profile of Brazilian lung adenocarcinoma unveils association of EGFR mutations with high Asian ancestry and independent prognostic role of KRAS mutations","volume":"9","author":"Leal","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1038\/nrc2088","article-title":"Epidermal growth factor receptor mutations in lung cancer","volume":"7","author":"Sharma","year":"2007","journal-title":"Nat. Rev. Cancer"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3196","DOI":"10.1158\/1078-0432.CCR-14-2594","article-title":"Detection and dynamic changes of EGFR mutations from circulating tumor DNA as a predictor of survival outcomes in NSCLC patients treated with first-line intercalated erlotinib and chemotherapy","volume":"21","author":"Mok","year":"2015","journal-title":"Clin. Cancer Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1016\/j.apsb.2015.07.001","article-title":"Mechanisms of resistance to EGFR tyrosine kinase inhibitors","volume":"5","author":"Huang","year":"2015","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4392s","DOI":"10.1158\/1078-0432.CCR-06-0096","article-title":"\u201cOncogenic shock\u201d: Explaining oncogene addiction through differential signal attenuation","volume":"12","author":"Sharma","year":"2006","journal-title":"Clin. Cancer Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/j.semcancer.2004.04.005","article-title":"Oncogenic growth factor receptors: Implications for signal transduction therapy","volume":"14","author":"Mosesson","year":"2004","journal-title":"Semin. Cancer Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"S24","DOI":"10.1038\/onc.2009.198","article-title":"Activating and resistance mutations of EGFR in non-small-cell lung cancer: Role in clinical response to EGFR tyrosine kinase inhibitors","volume":"28","author":"Gazdar","year":"2009","journal-title":"Oncogene"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Su, J., Zhong, W.-Z., Zhang, X., Huang, Y., Yan, H., Yang, J., Dong, Z., Xie, Z., Zhou, Q., and Huang, X. (2017). Molecular characteristics and clinical outcomes of EGFR exon 19 indel subtypes to EGFR TKIs in NSCLC patients. Oncotarget, 8.","DOI":"10.18632\/oncotarget.22768"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.semcancer.2019.09.015","article-title":"Rare epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer","volume":"61","author":"Harrison","year":"2020","journal-title":"Semin. Cancer Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.ejphar.2015.02.029","article-title":"Pharmacogenomics and targeted therapy of cancer: Focusing on non-small cell lung cancer","volume":"754","author":"Haghgoo","year":"2015","journal-title":"Eur. J. Pharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5305","DOI":"10.1158\/1078-0432.CCR-15-1046","article-title":"EGFR exon 18 mutations in lung cancer: Molecular predictors of augmented sensitivity to afatinib or neratinib as compared with first-or third-generation TKIs","volume":"21","author":"Kobayashi","year":"2015","journal-title":"Clin. Cancer Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1016\/j.jtho.2018.01.003","article-title":"Computational analysis of epidermal growth factor receptor mutations predicts differential drug sensitivity profiles toward kinase inhibitors","volume":"13","author":"Akula","year":"2018","journal-title":"J. Thorac. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5764","DOI":"10.1158\/1078-0432.CCR-06-0714","article-title":"Analysis of epidermal growth factor receptor gene mutation in patients with non\u2013small cell lung cancer and acquired resistance to gefitinib","volume":"12","author":"Kosaka","year":"2006","journal-title":"Clin. Cancer Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.canlet.2018.03.005","article-title":"Primary and acquired EGFR T790M-mutant NSCLC patients identified by routine mutation testing show different characteristics but may both respond to osimertinib treatment","volume":"423","author":"Li","year":"2018","journal-title":"Cancer Lett."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2070","DOI":"10.1073\/pnas.0709662105","article-title":"The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP","volume":"105","author":"Yun","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"637","DOI":"10.2217\/fon-2018-0736","article-title":"Tumor clonality and resistance mechanisms in EGFR mutation-positive non-small-cell lung cancer: Implications for therapeutic sequencing","volume":"15","author":"Kohsaka","year":"2019","journal-title":"Future Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"6169","DOI":"10.1158\/1078-0432.CCR-11-3265","article-title":"Molecular epidemiology of EGFR and KRAS mutations in 3026 lung adenocarcinomas: Higher susceptibility of women to smoking-related KRAS-mutant cancers","volume":"18","author":"Dogan","year":"2012","journal-title":"Clin. Cancer Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1146\/annurev-pathol-011110-130206","article-title":"EGFR mutations and lung cancer","volume":"6","author":"Shepherd","year":"2011","journal-title":"Annu. Rev. Pathol. Mech. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3750","DOI":"10.1158\/1078-0432.CCR-04-1981","article-title":"Mutation in the tyrosine kinase domain of epidermal growth factor receptor is a predictive and prognostic factor for gefitinib treatment in patients with non\u2013small cell lung cancer","volume":"11","author":"Chou","year":"2005","journal-title":"Clin. Cancer Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"216ra177","DOI":"10.1126\/scitranslmed.3007205","article-title":"Structural, biochemical, and clinical characterization of epidermal growth factor receptor (EGFR) exon 20 insertion mutations in lung cancer","volume":"5","author":"Yasuda","year":"2013","journal-title":"Sci. Transl. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1038\/s41392-019-0038-9","article-title":"Targeting EGFR exon 20 insertion mutations in non-small cell lung cancer","volume":"4","author":"Vyse","year":"2019","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1815","DOI":"10.3390\/cancers7030864","article-title":"The evolution of therapies in non-small cell lung cancer","volume":"7","author":"Boolell","year":"2015","journal-title":"Cancers"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"103811","DOI":"10.1016\/j.bioorg.2020.103811","article-title":"A review on progression of epidermal growth factor receptor (EGFR) inhibitors as an efficient approach in cancer targeted therapy","volume":"99","author":"Ayati","year":"2020","journal-title":"Bioorgan. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Aran, V., and Omerovic, J. (2019). Current Approaches in NSCLC Targeting K-RAS and EGFR. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20225701"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1700","DOI":"10.1056\/NEJMoa1413654","article-title":"Rociletinib in EGFR-mutated non\u2013small-cell lung cancer","volume":"372","author":"Sequist","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e447","DOI":"10.1016\/S1470-2045(15)00246-6","article-title":"Treatment approaches for EGFR-inhibitor-resistant patients with non-small-cell lung cancer","volume":"16","author":"Tan","year":"2015","journal-title":"Lancet Oncol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"6580","DOI":"10.1021\/acs.jmedchem.5b00840","article-title":"Challenges and perspectives on the development of small-molecule EGFR inhibitors against T790M-mediated resistance in non-small-cell lung cancer: Miniperspective","volume":"59","author":"Song","year":"2016","journal-title":"J. Med. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.canlet.2016.11.008","article-title":"EAI045: The fourth-generation EGFR inhibitor overcoming T790M and C797S resistance","volume":"385","author":"Wang","year":"2017","journal-title":"Cancer Lett."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1038\/nrc3580","article-title":"Mechanistic insight into ALK receptor tyrosine kinase in human cancer biology","volume":"13","author":"Hallberg","year":"2013","journal-title":"Nat. Rev. Cancer"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Wu, W., Haderk, F., and Bivona, T.G. (2017). Non-Canonical Thinking for Targeting ALK-Fusion Onco-Proteins in Lung Cancer. Cancers, 9.","DOI":"10.3390\/cancers9120164"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1007\/s00018-015-2117-6","article-title":"Molecular mechanisms that underpin EML4-ALK driven cancers and their response to targeted drugs","volume":"73","author":"Bayliss","year":"2016","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1724","DOI":"10.1158\/1541-7786.MCR-18-0171","article-title":"ALK fusion partners impact response to ALK inhibition: Differential effects on sensitivity, cellular phenotypes, and biochemical properties","volume":"16","author":"Childress","year":"2018","journal-title":"Mol. Cancer Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1038\/nature05945","article-title":"Identification of the transforming EML4\u2013ALK fusion gene in non-small-cell lung cancer","volume":"448","author":"Soda","year":"2007","journal-title":"Nature"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1200\/JCO.2017.76.2294","article-title":"Impact of EML4-ALK variant on resistance mechanisms and clinical outcomes in ALK-positive lung cancer","volume":"36","author":"Lin","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"757490","DOI":"10.1155\/2013\/757490","article-title":"Targeted resequencing reveals ALK fusions in non-small cell lung carcinomas detected by FISH, immunohistochemistry, and real-time RT-PCR: A comparison of four methods","volume":"2013","author":"Tuononen","year":"2013","journal-title":"BioMed Res. Int."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3383","DOI":"10.1200\/JCO.2015.65.8732","article-title":"Differential Crizotinib Response Duration Among ALK Fusion Variants in ALK-Positive Non-Small-Cell Lung Cancer","volume":"34","author":"Yoshida","year":"2016","journal-title":"J. Clin. Oncol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/s11864-015-0367-z","article-title":"New Treatment Options for ALK-Rearranged Non-Small Cell Lung Cancer","volume":"16","author":"Cameron","year":"2015","journal-title":"Curr. Treat. Options Oncol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1177\/1758834015617355","article-title":"ALK inhibitors in non-small cell lung cancer: The latest evidence and developments","volume":"8","author":"Sullivan","year":"2016","journal-title":"Ther. Adv. Med. Oncol."},{"key":"ref_46","first-page":"145","article-title":"Personalized treatment options for ALK-positive metastatic non-small-cell lung cancer: Potential role for Ceritinib","volume":"8","author":"Shackelford","year":"2015","journal-title":"Pharm. Pers. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"4408","DOI":"10.1158\/0008-5472.CAN-06-4443","article-title":"An orally available small-molecule inhibitor of c-Met, PF-2341066, exhibits cytoreductive antitumor efficacy through antiproliferative and antiangiogenic mechanisms","volume":"67","author":"Zou","year":"2007","journal-title":"Cancer Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2029","DOI":"10.1158\/1078-0432.CCR-13-3077","article-title":"US Food and Drug Administration approval: Crizotinib for treatment of advanced or metastatic non\u2013small cell lung cancer that is anaplastic lymphoma kinase positive","volume":"20","author":"Malik","year":"2014","journal-title":"Clin. Cancer Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1158\/2159-8290.CD-13-0846","article-title":"The ALK inhibitor ceritinib overcomes crizotinib resistance in non-small cell lung cancer","volume":"4","author":"Friboulet","year":"2014","journal-title":"Cancer Discov."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12943-018-0810-4","article-title":"The function and therapeutic targeting of anaplastic lymphoma kinase (ALK) in non-small cell lung cancer (NSCLC)","volume":"17","author":"Golding","year":"2018","journal-title":"Mol. Cancer"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1370","DOI":"10.1200\/JCO.18.02236","article-title":"ALK resistance mutations and efficacy of lorlatinib in advanced anaplastic lymphoma kinase-positive non\u2013small-cell lung cancer","volume":"37","author":"Shaw","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"S882","DOI":"10.21037\/jtd.2018.03.81","article-title":"Liquid biopsy for lung cancer early detection","volume":"10","author":"Santarpia","year":"2018","journal-title":"J. Thorac. Dis."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1158\/2159-8290.CD-15-1483","article-title":"Clinical applications of circulating tumor cells and circulating tumor DNA as liquid biopsy","volume":"6","author":"Pantel","year":"2016","journal-title":"Cancer Discov."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"i38","DOI":"10.1093\/annonc\/mdx706","article-title":"Are liquid biopsies a surrogate for tissue EGFR testing?","volume":"29","author":"Goldman","year":"2018","journal-title":"Ann. Oncol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1111\/joim.12897","article-title":"Cell-free tumour DNA testing for early detection of cancer\u2014A potential future tool","volume":"286","author":"Barbany","year":"2019","journal-title":"J. Intern. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"S171","DOI":"10.21037\/tcr.2017.10.10","article-title":"Clinical relevance of size selection of circulating DNA","volume":"7","author":"Grunt","year":"2017","journal-title":"Transl. Cancer Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e1501332","DOI":"10.1126\/sciadv.1501332","article-title":"Obesity-induced DNA released from adipocytes stimulates chronic adipose tissue inflammation and insulin resistance","volume":"2","author":"Nishimoto","year":"2016","journal-title":"Sci. Adv."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1002\/pd.3919","article-title":"A multi-factorial relationship exists between total circulating cell-free DNA levels and maternal BMI","volume":"32","author":"Vora","year":"2012","journal-title":"Prenat. Diagn."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2093","DOI":"10.1056\/NEJMoa1801946","article-title":"Nivolumab plus Ipilimumab in Lung Cancer with a High Tumor Mutational Burden","volume":"378","author":"Hellmann","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"505","DOI":"10.21037\/tlcr.2016.10.08","article-title":"Next generation sequencing techniques in liquid biopsy: Focus on non-small cell lung cancer patients","volume":"5","author":"Malapelle","year":"2016","journal-title":"Transl. Lung Cancer Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/j.lungcan.2015.10.004","article-title":"EGFR mutation detection in ctDNA from NSCLC patient plasma: A cross-platform comparison of leading technologies to support the clinical development of AZD9291","volume":"90","author":"Thress","year":"2015","journal-title":"Lung Cancer"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"3375","DOI":"10.1200\/JCO.2016.66.7162","article-title":"Association Between Plasma Genotyping and Outcomes of Treatment With Osimertinib (AZD9291) in Advanced Non-Small-Cell Lung Cancer","volume":"34","author":"Oxnard","year":"2016","journal-title":"J. Clin. Oncol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1016\/j.jtho.2017.04.003","article-title":"Plasma ctDNA Analysis for Detection of the EGFR T790M Mutation in Patients with Advanced Non-Small Cell Lung Cancer","volume":"12","author":"Jenkins","year":"2017","journal-title":"J. Thorac. Oncol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.cllc.2018.03.015","article-title":"Dynamics of EGFR Mutation Load in Plasma for Prediction of Treatment Response and Disease Progression in Patients With EGFR-Mutant Lung Adenocarcinoma","volume":"19","author":"Taus","year":"2018","journal-title":"Clin. Lung Cancer"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"S1323","DOI":"10.21037\/jtd.2017.06.144","article-title":"Urine test for EGFR analysis in patients with non-small cell lung cancer","volume":"9","author":"Franovic","year":"2017","journal-title":"J. Thorac. Dis."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1196\/annals.1448.015","article-title":"Transrenal nucleic acids: From proof of principle to clinical tests","volume":"1137","author":"Melkonyan","year":"2008","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Li, F., Wei, F., Huang, W.L., Lin, C.C., Li, L., Shen, M.M., Yan, Q., Liao, W., Chia, D., and Tu, M. (2020). Ultra-Short Circulating Tumor DNA (usctDNA) in Plasma and Saliva of Non-Small Cell Lung Cancer (NSCLC) Patients. Cancers, 12.","DOI":"10.3390\/cancers12082041"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1002\/cam4.1935","article-title":"Differences in the genomic profiles of cell-free DNA between plasma, sputum, urine, and tumor tissue in advanced NSCLC","volume":"8","author":"Wu","year":"2019","journal-title":"Cancer Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"4716","DOI":"10.1158\/1078-0432.CCR-17-0454","article-title":"Monitoring Daily Dynamics of Early Tumor Response to Targeted Therapy by Detecting Circulating Tumor DNA in Urine","volume":"23","author":"Husain","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1690","DOI":"10.1016\/j.jtho.2016.05.035","article-title":"A Highly Sensitive and Quantitative Test Platform for Detection of NSCLC EGFR Mutations in Urine and Plasma","volume":"11","author":"Reckamp","year":"2016","journal-title":"J. Thorac. Oncol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s40164-016-0052-3","article-title":"Non-invasive urine testing of EGFR activating mutation and T790M resistance mutation in non-small cell lung cancer","volume":"5","author":"Berz","year":"2015","journal-title":"Exp. Hematol. Oncol."},{"key":"ref_72","first-page":"3581","article-title":"Non-invasive detection of EGFR and TP53 mutations through the combination of plasma, urine and sputum in advanced non-small cell lung cancer","volume":"18","author":"Wu","year":"2019","journal-title":"Oncol. Lett."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1016\/j.jmoldx.2020.04.208","article-title":"Sputum Cell-Free DNA: Valued Surrogate Sample for Detection of EGFR Mutation in Patients with Advanced Lung Adenocarcinoma","volume":"22","author":"Wang","year":"2020","journal-title":"J. Mol. Diagn."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1111\/cyt.12517","article-title":"A Combined test using both cell sediment and supernatant cell-free DNA in pleural effusion shows increased sensitivity in detecting activating EGFR mutation in lung cancer patients","volume":"29","author":"Kawahara","year":"2018","journal-title":"Cytopathology"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Lee, J.S., Hur, J.Y., Kim, I.A., Kim, H.J., Choi, C.M., Lee, J.C., Kim, W.S., and Lee, K.Y. (2018). Liquid biopsy using the supernatant of a pleural effusion for EGFR genotyping in pulmonary adenocarcinoma patients: A comparison between cell-free DNA and extracellular vesicle-derived DNA. BMC Cancer, 18.","DOI":"10.1186\/s12885-018-5138-3"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.lungcan.2019.08.004","article-title":"Cytological-negative pleural effusion can be an alternative liquid biopsy media for detection of EGFR mutation in NSCLC patients","volume":"136","author":"Song","year":"2019","journal-title":"Lung Cancer"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"5532","DOI":"10.7150\/thno.34070","article-title":"Tumor-derived DNA from pleural effusion supernatant as a promising alternative to tumor tissue in genomic profiling of advanced lung cancer","volume":"9","author":"Tong","year":"2019","journal-title":"Theranostics"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2598","DOI":"10.1158\/1535-7163.MCT-17-0386","article-title":"Tumor Mutational Burden as an Independent Predictor of Response to Immunotherapy in Diverse Cancers","volume":"16","author":"Goodman","year":"2017","journal-title":"Mol. Cancer Ther."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1038\/s41374-020-0459-7","article-title":"Reliability of liquid biopsy analysis: An inter-laboratory comparison of circulating tumor DNA extraction and sequencing with different platforms","volume":"100","author":"Koessler","year":"2020","journal-title":"Lab. Investig."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"151","DOI":"10.14740\/wjon1167","article-title":"EGFR mutation detection and its association with clinicopathological characters of lung cancer patients","volume":"9","author":"Gaur","year":"2018","journal-title":"World J. Oncol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.lungcan.2019.03.018","article-title":"Comparison of ALK detection by FISH, IHC and NGS to predict benefit from crizotinib in advanced non-small-cell lung cancer","volume":"131","author":"Lin","year":"2019","journal-title":"Lung Cancer"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1660","DOI":"10.1111\/cas.13068","article-title":"Tumor volume determines the feasibility of cell-free DNA sequencing for mutation detection in non-small cell lung cancer","volume":"107","author":"Ohira","year":"2016","journal-title":"Cancer Sci."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Wu, Y.-C., Chang, I.-C., Wang, C.-L., Chen, T.-D., Chen, Y.-T., Liu, H.-P., Chu, Y., Chiu, Y.-T., Wu, T.-H., and Chou, L.-H. (2013). Comparison of IHC, FISH and RT-PCR methods for detection of ALK rearrangements in 312 non-small cell lung cancer patients in Taiwan. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0070839"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"8604","DOI":"10.1021\/ac202028g","article-title":"High-throughput droplet digital PCR system for absolute quantitation of DNA copy number","volume":"83","author":"Hindson","year":"2011","journal-title":"Anal. Chem."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"136ra168","DOI":"10.1126\/scitranslmed.3003726","article-title":"Noninvasive identification and monitoring of cancer mutations by targeted deep sequencing of plasma DNA","volume":"4","author":"Forshew","year":"2012","journal-title":"Sci. Transl. Med."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/nrg.2017.117","article-title":"Enhancing the accuracy of next-generation sequencing for detecting rare and subclonal mutations","volume":"19","author":"Salk","year":"2018","journal-title":"Nat. Rev. Genet."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1007\/s12094-019-02211-x","article-title":"Liquid biopsy in oncology: A consensus statement of the Spanish Society of Pathology and the Spanish Society of Medical Oncology","volume":"22","author":"Remon","year":"2020","journal-title":"Clin. Transl. Oncol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1038\/nrclinonc.2017.14","article-title":"Integrating liquid biopsies into the management of cancer","volume":"14","author":"Siravegna","year":"2017","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"631","DOI":"10.3389\/fonc.2019.00631","article-title":"Five Technologies for Detecting the EGFR T790M Mutation in the Circulating Cell-Free DNA of Patients With Non-small Cell Lung Cancer: A Comparison","volume":"9","author":"Chen","year":"2019","journal-title":"Front. Oncol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1883","DOI":"10.1093\/annonc\/mdv270","article-title":"First-line erlotinib versus gemcitabine\/cisplatin in patients with advanced EGFR mutation-positive non-small-cell lung cancer: Analyses from the phase III, randomized, open-label, ENSURE study","volume":"26","author":"Wu","year":"2015","journal-title":"Ann. Oncol."},{"key":"ref_91","first-page":"584","article-title":"Circulating DNA in diagnosis and monitoring EGFR gene mutations in advanced non-small cell lung cancer","volume":"4","author":"Bordi","year":"2015","journal-title":"Transl. Lung Cancer Res."},{"key":"ref_92","first-page":"i29","article-title":"Determining the prevalence of EGFR mutations in Asian and Russian patients (pts) with advanced non-small-cell lung cancer (aNSCLC) of adenocarcinoma (ADC) and non-ADC histology: IGNITE study","volume":"26","author":"Han","year":"2015","journal-title":"Ann. Oncol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1682","DOI":"10.1016\/j.jtho.2016.05.036","article-title":"ctDNA Determination of EGFR Mutation Status in European and Japanese Patients with Advanced NSCLC: The ASSESS Study","volume":"11","author":"Reck","year":"2016","journal-title":"J. Thorac. Oncol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1097\/JTO.0000000000000263","article-title":"Gefitinib treatment in EGFR mutated caucasian NSCLC: Circulating-free tumor DNA as a surrogate for determination of EGFR status","volume":"9","author":"Douillard","year":"2014","journal-title":"J. Thorac. Oncol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"v474","DOI":"10.1093\/annonc\/mdx380.033","article-title":"Detection of EGFR T790M in Asia-Pacific patients (pts) with EGFR mutation-positive advanced non-small cell lung cancer (NSCLC): Circulating tumour (ct) DNA analysis across 3 platforms","volume":"28","author":"Zhou","year":"2017","journal-title":"Ann. Oncol."},{"key":"ref_96","first-page":"v484","article-title":"CNS response to osimertinib in Asian-Pacific patients (pts) with T790M-positive advanced NSCLC: Data from an open-label Phase II trial (AURA17)","volume":"28","author":"Zhou","year":"2017","journal-title":"Ann. Oncol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/s13046-018-0735-1","article-title":"5\u2019\/3\u2019 imbalance strategy to detect ALK fusion genes in circulating tumor RNA from patients with non-small cell lung cancer","volume":"37","author":"Tong","year":"2018","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"2758","DOI":"10.1158\/1078-0432.CCR-17-2588","article-title":"Clinical Utility of Cell-Free DNA for the Detection of ALK Fusions and Genomic Mechanisms of ALK Inhibitor Resistance in Non-Small Cell Lung Cancer","volume":"24","author":"McCoach","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1016\/j.cllc.2017.04.013","article-title":"Detection of ALK and KRAS Mutations in Circulating Tumor DNA of Patients With Advanced ALK-Positive NSCLC With Disease Progression During Crizotinib Treatment","volume":"18","author":"Bordi","year":"2017","journal-title":"Clin. Lung Cancer"},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Lanman, R.B., Mortimer, S.A., Zill, O.A., Sebisanovic, D., Lopez, R., Blau, S., Collisson, E.A., Divers, S.G., Hoon, D.S., and Kopetz, E.S. (2015). Analytical and Clinical Validation of a Digital Sequencing Panel for Quantitative, Highly Accurate Evaluation of Cell-Free Circulating Tumor DNA. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0140712"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/8\/3815\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:34:12Z","timestamp":1760362452000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/8\/3815"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,7]]},"references-count":100,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2021,4]]}},"alternative-id":["ijms22083815"],"URL":"https:\/\/doi.org\/10.3390\/ijms22083815","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,7]]}}}