Liquid Biopsy: A New, Non-Invasive Early Diagnostic and Prognostic Tool in Oncology

Authors

  • Ciro Comparetto Division of Obstetrics and Gynecology, San Paolo Private Clinic, Pistoia, Italy
  • Franco Borruto Professor of Obstetrics and Gynecology, Consultant in Health Policy of the Government of Monaco, Principality of Monaco

DOI:

https://doi.org/10.30683/1929-2279.2020.09.06

Keywords:

Liquid biopsy, cancer, gynecological oncology, cell-free DNA, circulating tumor cells, precision oncology, early diagnosis.

Abstract

Cancer is essentially a genetic disease. Neoplastic progression consists of a subsequent series of genetic alterations that cumulate. In the bloodstream of an affected subject, circulating tumor cells (CTC) and/or small deoxy-ribonucleic acid (DNA) fragments, known as    circulating tumor DNA (ctDNA), can be found as a consequence of cancer cells death. Cell-free circulating DNA (cfDNA) consists of small fragments of DNA that are found free in plasma or serum, but also in other body fluids. The term liquid biopsy (LB) describes a highly sensitive method (based on a simple sampling of peripheral blood) for the isolation and analysis of cfDNA, which can also contain ctDNA and CTC. Its purpose is to look for cancer cells or portions of their DNA that are circulating in the blood. LB can be used to help find cancer in an early stage. It also has the additional advantage of being largely non-invasive and, therefore, being done more frequently, allowing better tumor and genetic mutations tracking. It can also be used to validate the efficacy of a drug for cancer treatment by taking multiple samples of LB within a few weeks. This technology can also be beneficial for patients after treatment to control relapse. The aim of this work is to give an overview of this technique, from its history, state-of-the-art, and methodology of execution, to its applications in oncology and with a hint to the gynecological field.  

References

Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C, Edkins S, O'Meara S, Vastrik I, Schmidt EE, Avis T, Barthorpe S, Bhamra G, Buck G, Choudhury B, Clements J, Cole J, Dicks E, Forbes S, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jenkinson A, Jones D, Menzies A, Mironenko T, Perry J, Raine K, Richardson D, Shepherd R, Small A, Tofts C, Varian J, Webb T, West S, Widaa S, Yates A, Cahill DP, Louis DN, Goldstraw P, Nicholson AG, Brasseur F, Looijenga L, Weber BL, Chiew YE, DeFazio A, Greaves MF, Green AR, Campbell P, Birney E, Easton DF, Chenevix-Trench G, Tan MH, Khoo SK, Teh BT, Yuen ST, Leung SY, Wooster R, Futreal PA, Stratton MR. Patterns of somatic mutation in human cancer genomes. Nature 2007; 446: 153-8. https://doi.org/10.1038/nature05610

Stephens PJ, Tarpey PS, Davies H, Van Loo P, Greenman C, Wedge DC, Nik-Zainal S, Martin S, Varela I, Bignell GR, Yates LR, Papaemmanuil E, Beare D, Butler A, Cheverton A, Gamble J, Hinton J, Jia M, Jayakumar A, Jones D, Latimer C, Lau KW, McLaren S, McBride DJ, Menzies A, Mudie L, Raine K, Rad R, Chapman MS, Teague J, Easton D, Langerød A; Oslo Breast Cancer Consortium (OSBREAC), Lee MT, Shen CY, Tee BT, Huimin BW, Broeks A, Vargas AC, Turashvili G, Martens J, Fatima A, Miron P, Chin SF, Thomas G, Boyault S, Mariani O, Lakhani SR, van de Vijver M, van 't Veer L, Foekens J, Desmedt C, Sotiriou C, Tutt A, Caldas C, Reis-Filho JS, Aparicio SA, Salomon AV, Børresen-Dale AL, Richardson AL, Campbell PJ, Futreal PA, Stratton MR. The landscape of cancer genes and mutational processes in breast cancer. Nature 2012; 486: 400-4. https://doi.org/10.1038/nature11017

Diaz LA Jr, Bardelli A. Liquid biopsies: genotyping circulating tumor DNA. J Clin Oncol 2014; 32: 579-86. https://doi.org/10.1200/JCO.2012.45.2011

Heitzer E, Ulz P, Geigl JB. Circulating tumor DNA as a liquid biopsy for cancer. Clin Chem 2015; 6: 112-23. https://doi.org/10.1373/clinchem.2014.222679

Lebofsky R, Decraene C, Bernard V, Kamal M, Blin A, Leroy Q, Rio Frio T, Pierron G, Callens C, Bieche I, Saliou A, Madic J, Rouleau E, Bidard FC, Lantz O, Stern MH, Le Tourneau C, Pierga JY. Circulating tumor DNA as a non-invasive substitute to metastasis biopsy for tumor genotyping and personalized medicine in a prospective trial across all tumor types. Mol Oncol 2015; 9: 783-90. https://doi.org/10.1016/j.molonc.2014.12.003

Esposito A, Bardelli A, Criscitiello C, Colombo N, Gelao L, Fumagalli L, Minchella I, Locatelli M, Goldhirsch A, Curigliano G. Monitoring tumor-derived cell-free DNA in patients with solid tumors: clinical perspectives and research opportunities. Cancer Treat Rev 2014; 40: 648-55. https://doi.org/10.1016/j.ctrv.2013.10.003

Kidess E, Heirich K, Wiggin M, Vysotskaia V, Visser BC, Marziali A, Wiedenmann B, Norton JA, Lee M, Jeffrey SS, Poultsides GA. Mutation profiling of tumor DNA from plasma and tumor tissue of colorectal cancer patients with a novel, high-sensitivity multiplexed mutation detection platform. Oncotarget 2015; 6: 2549-61. https://doi.org/10.18632/oncotarget.3041

Forshew T, Murtaza M, Parkinson C, Gale D, Tsui DW, Kaper F, Dawson SJ, Piskorz AM, Jimenez-Linan M, Bentley D, Hadfield J, May AP, Caldas C, Brenton JD, Rosenfeld N. Noninvasive identification and monitoring of cancer mutations by targeted deep sequencing of plasma DNA. Sci Transl Med 2012; 4: 136ra68. https://doi.org/10.1126/scitranslmed.3003726

Nascimento da Silva M, Sicchieri LB, Rodrigues de Oliveira Silva F, Andrade MF; Courrol LC. Liquid biopsy of atherosclerosis using protoporphyrin IX as a biomarker. The Analyst 2014; 139: 1383-8. https://doi.org/10.1039/c3an01945d

Aarthy R, Mani S, Velusami S, Sundarsingh S, Rajkumar T. Role of Circulating Cell-Free DNA in Cancers. Mol Diagn Ther 2015; 19: 339-50. https://doi.org/10.1007/s40291-015-0167-y

Chaudhuri AA, Binkley MS, Osmundson EC, Alizadeh AA, Diehn M. Predicting Radiotherapy Responses and Treatment Outcomes Through Analysis of Circulating Tumor DNA. Semin Radiat Oncol 2015; 25: 305-12. https://doi.org/10.1016/j.semradonc.2015.05.001

Ignatiadis M, Lee M, Jeffrey SS. Circulating Tumor Cells and Circulating Tumor DNA: Challenges and Opportunities on the Path to Clinical Utility. Clin Cancer Res 2015; 21: 4786-800. https://doi.org/10.1158/1078-0432.CCR-14-1190

Polivka J Jr, Pesta M, Janku F. Testing for oncogenic molecular aberrations in cell-free DNA-based liquid biopsies in the clinic: are we there yet? Expert Rev Mol Diagn 2015; 15: 1631-44. https://doi.org/10.1586/14737159.2015.1110021

Diehl F, Schmidt K, Choti MA, Romans K, Goodman S, Li M, Thornton K, Agrawal N, Sokoll L, Szabo SA, Kinzler KW, Vogelstein B, Diaz LA Jr. Circulating mutant DNA to assess tumor dynamics. Nat Med 2008; 14: 985-90. https://doi.org/10.1038/nm.1789

Diehl F, Li M, Dressman D, He Y, Shen D, Szabo S, Diaz LA Jr, Goodman SN, David KA, Juhl H, Kinzler KW, Vogelstein B. Detection and quantification of mutations in the plasma of patients with colorectal tumors. Proc Natl Acad Sci U S A 2005; 102: 16368-73. https://doi.org/10.1073/pnas.0507904102

Fan HC, Blumenfeld YJ, Chitkara U, Hudgins L, Quake SR. Noninvasive diagnosis of fetal aneuploidy by shotgun sequencing DNA from maternal blood. Proc Natl Acad Sci U S A 2008; 105: 16266-71. https://doi.org/10.1073/pnas.0808319105

Jahr S, Hentze H, Englisch S, Hardt D, Fackelmayer FO, Hesch RD, Knippers R. DNA fragments in the blood plasma of cancer patients: quantitations and evidence for their origin from apoptotic and necrotic cells. Cancer Res 2001; 61: 1659-65. PMID: 11245480.

Mouliere F, Robert B, Arnau Peyrotte E, Del Rio M, Ychou M, Molina F, Gongora C, Thierry AR. High fragmentation characterizes tumour-derived circulating DNA. PLoS One 2011; 6: e23418. https://doi.org/10.1371/journal.pone.0023418

Holdhoff M, Schmidt K, Donehower R, Diaz LA Jr. Analysis of circulating tumor DNA to confirm somatic KRAS mutations. J Natl Cancer Inst 2009; 101: 1284-5. https://doi.org/10.1093/jnci/djp240

Newman AM, Bratman SV, To J, Wynne JF, Eclov NC, Modlin LA, Liu CL, Neal JW, Wakelee HA, Merritt RE, Shrager JB, Loo BW Jr, Alizadeh AA, Diehn M. An ultrasensitive method for quantitating circulating tumor DNA with broad patient coverage. Nat Med 2014; 20: 548-54. https://doi.org/10.1038/nm.3519

Huang C, Quinn D, Sadovsky Y, Suresh S, Hsia KJ. Formation and size distribution of self-assembled vesicles. Proc Natl Acad Sci U S A 2017; 114: 2910-5. https://doi.org/10.1073/pnas.1702065114

Jie XX, Zhang XY, Xu CJ. Epithelial-to-mesenchymal transition, circulating tumor cells and cancer metastasis: Mechanisms and clinical applications. Oncotarget 2017; 8: 81558-71. https://doi.org/10.18632/oncotarget.18277

Stoecklein NH, Fischer JC, Niederacher D, Terstappen LW. Challenges for CTC-based liquid biopsies: low CTC frequency and diagnostic leukapheresis as a potential solution. Expert Rev Mol Diagn 2016; 16: 147-64. https://doi.org/10.1586/14737159.2016.1123095

Pös O, Biró O, Szemes T, Nagy B. Circulating cell-free nucleic acids: characteristics and applications. Eur J Hum Genet 2018; 26: 937-45. https://doi.org/10.1038/s41431-018-0132-4

Pyykkö OT, Lumela M, Rummukainen J, Nerg O, Seppälä TT, Herukka SK, Koivisto AM, Alafuzoff I, Puli L, Savolainen S, Soininen H, Jääskeläinen JE, Hiltunen M, Zetterberg H, Leinonen V. Cerebrospinal Fluid Biomarker and Brain Biopsy Findings in Idiopathic Normal Pressure Hydrocephalus. PLoS One 2014; 9: e91974. https://doi.org/10.1371/journal.pone.0091974

Jovelet C, Ileana E, Le Deley MC, Motté N, Rosellini S, Romero A, Lefebvre C, Pedrero M, Pata-Merci N, Droin N, Deloger M, Massard C, Hollebecque A, Ferté C, Boichard A, Postel-Vinay S, Ngo-Camus M, De Baere T, Vielh P, Scoazec JY, Vassal G, Eggermont A, André F, Soria JC, Lacroix L. Circulating Cell-Free Tumor DNA Analysis of 50 Genes by Next-Generation Sequencing in the Prospective MOSCATO Trial. Clin Cancer Res 2016; 22: 2960-8. https://doi.org/10.1158/1078-0432.CCR-15-2470

Gerlinger M, Rowan AJ, Horswell S, Math M, Larkin J, Endesfelder D, Gronroos E, Martinez P, Matthews N, Stewart A, Tarpey P, Varela I, Phillimore B, Begum S, McDonald NQ, Butler A, Jones D, Raine K, Latimer C, Santos CR, Nohadani M, Eklund AC, Spencer-Dene B, Clark G, Pickering L, Stamp G, Gore M, Szallasi Z, Downward J, Futreal PA, Swanton C. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med 2012; 366: 883-92. https://doi.org/10.1056/NEJMoa1113205

Hiley C, de Bruin EC, McGranahan N, Swanton C. Deciphering intratumor heterogeneity and temporal acquisition of driver events to refine precision medicine. Genome Biol 2014; 15: 453. https://doi.org/10.1186/s13059-014-0453-8

Ichihara E, Lovly CM. Shades of T790M: Intratumor Heterogeneity in EGFR-Mutant Lung Cancer. Cancer Discov 2015; 5: 694-6. https://doi.org/10.1158/2159-8290.CD-15-0616

Gerlinger M, Rowan AJ, Horswell S, Math M, Larkin J, Endesfelder D, Gronroos E, Martinez P, Matthews N, Stewart A, Tarpey P, Varela I, Phillimore B, Begum S, McDonald NQ, Butler A, Jones D, Raine K, Latimer C, Santos CR, Nohadani M, Eklund AC, Spencer-Dene B, Clark G, Pickering L, Stamp G, Gore M, Szallasi Z, Downward J, Futreal PA, Swanton C. The life history of 21 breast cancers. Cell 2012; 149: 994-1007. https://doi.org/10.1016/j.cell.2012.04.023

Piotrowska Z, Niederst MJ, Karlovich CA, Wakelee HA, Neal JW, Mino-Kenudson M, Fulton L, Hata AN, Lockerman EL, Kalsy A, Digumarthy S, Muzikansky A, Raponi M, Garcia AR, Mulvey HE, Parks MK, DiCecca RH, Dias-Santagata D, Iafrate AJ, Shaw AT, Allen AR, Engelman JA, Sequist LV. Heterogeneity Underlies the Emergence of EGFRT790 Wild-Type Clones Following Treatment of T790M-Positive Cancers with a Third-Generation EGFR Inhibitor. Cancer Discov 2015; 5: 713-22. https://doi.org/10.1158/2159-8290.CD-15-0399

Wang Y, Waters J, Leung ML, Unruh A, Roh W, Shi X, Chen K, Scheet P, Vattathil S, Liang H, Multani A, Zhang H, Zhao R, Michor F, Meric-Bernstam F, Navin NE. Clonal evolution in breast cancer revealed by single nucleus genome sequencing. Nature 2014; 512: 155-60. https://doi.org/10.1038/nature13600

Patel KM, Tsui DW. The translational potential of circulating tumour DNA in oncology. Clin Biochem 2015; 48: 957-61 https://doi.org/10.1016/j.clinbiochem.2015.04.005

Salvatore F. Liquid Biopsy or better “Molecular profile of circulating nucleic acids”: The New Frontier in Cancer Management. American Association for Clinical Chemistry, Washington DC, US, https://labtestsonline.it/news/la-biopsia-liquida-o-meglio-profilo-molecolare-di-acidi-nucleici-circolanti-la-nuova-frontiera; 2019

Rapado-González Ó, Majem B, Muinelo-Romay L, López-López R, Suarez-Cunqueiro MM. Cancer Salivary Biomarkers for Tumours Distant to the Oral Cavity. Int J Mol Sci 2016; 17.pii: E1531. https://doi.org/10.3390/ijms17091531

Majem B, Li F, Sun J, Wong DT. RNA Sequencing Analysis of Salivary Extracellular RNA. Methods Mol Biol 2017; 1537: 17-36. https://doi.org/10.1007/978-1-4939-6685-1_2

Rapado-González Ó, Majem B, Muinelo-Romay L, Álvarez-Castro A, Santamaría A, Gil-Moreno A, López-López R, Suárez-Cunqueiro MM. Human salivary microRNAs in Cancer. J Cancer 2018; 9: 638-49. https://doi.org/10.7150/jca.21180

Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, Teague J, Woffendin H, Garnett MJ, Bottomley W, Davis N, Dicks E, Ewing R, Floyd Y, Gray K, Hall S, Hawes R, Hughes J, Kosmidou V, Menzies A, Mould C, Parker A, Stevens C, Watt S, Hooper S, Wilson R, Jayatilake H, Gusterson BA, Cooper C, Shipley J, Hargrave D, Pritchard-Jones K, Maitland N, Chenevix-Trench G, Riggins GJ, Bigner DD, Palmieri G, Cossu A, Flanagan A, Nicholson A, Ho JW, Leung SY, Yuen ST, Weber BL, Seigler HF, Darrow TL, Paterson H, Marais R, Marshall CJ, Wooster R, Stratton MR, Futreal PA. Mutations of the BRAF gene in human cancer. Nature 2002; 417: 949-54. https://doi.org/10.1038/nature00766

Romero A, Acosta-Eyzaguirre D, Sanz J, Moreno F, Serrano G, Díaz-Rubio E, Caldés T, Garcia-Saenz JÁ. Identification of E545k mutation in plasma from a PIK3CA wild-type metastatic breast cancer patient by array-based digital polymerase chain reaction: Circulating-free DNA a powerful tool for biomarker testing in advance disease. Transl Res 2015; 166: 783-7. https://doi.org/10.1016/j.trsl.2015.04.010

Ascierto PA, Minor D, Ribas A, Lebbe C, O'Hagan A, Arya N, Guckert M, Schadendorf D, Kefford RF, Grob JJ, Hamid O, Amaravadi R, Simeone E, Wilhelm T, Kim KB, Long GV, Martin AM, Mazumdar J, Goodman VL, Trefzer U. Phase II trial (BREAK-2) of the BRAF inhibitor dabrafenib (GSK2118436) in patients with metastatic melanoma. J Clin Oncol 2013; 31: 3205-11. https://doi.org/10.1200/JCO.2013.49.8691

Rothschild SI. Targeted Therapies in Non-Small Cell Lung Cancer-Beyond EGFR and ALK. Cancers (Basel) 2015; 7: 930-49. https://doi.org/10.3390/cancers7020816

Heidary M, Auer M, Ulz P, Heitzer E, Petru E, Gasch C, Riethdorf S, Mauermann O, Lafer I, Pristauz G, Lax S, Pantel K, Geigl JB, Speicher MR. The dynamic range of circulating tumor DNA in metastatic breast cancer. Breast Cancer Res 2014; 16: 421. https://doi.org/10.1186/s13058-014-0421-y

Zill OA, Greene C, Sebisanovic D, Siew LM, Leng J, Vu M, Hendifar AE, Wang Z, Atreya CE, Kelley RK, Van Loon K, Ko AH, Tempero MA, Bivona TG, Munster PN, Talasaz A, Collisson EA. Cell-Free DNA Next-Generation Sequencing in Pancreatobiliary Carcinomas. Cancer Discov 2015; 5: 1040-8. https://doi.org/10.1158/2159-8290.CD-15-0274

Janku F, Angenendt P, Tsimberidou AM, Fu S, Naing A, Falchook GS, Hong DS, Holley VR, Cabrilo G, Wheler JJ, Piha-Paul SA, Zinner RG, Bedikian AY, Overman MJ, Kee BK, Kim KB, Kopetz ES, Luthra R, Diehl F, Meric-Bernstam F, Kurzrock R. Actionable mutations in plasma cell-free DNA in patients with advanced cancers referred for experimental targeted therapies. Oncotarget 2015; 6: 12809-21. https://doi.org/10.18632/oncotarget.3373

Tabernero J, Lenz HJ, Siena S, Sobrero A, Falcone A, Ychou M, Humblet Y, Bouché O, Mineur L, Barone C, Adenis A, Yoshino T, Goldberg RM, Sargent DJ, Wagner A, Laurent D, Teufel M, Jeffers M, Grothey A, Van Cutsem E. Analysis of circulating DNA and protein biomarkers to predict the clinical activity of regorafenib and assess prognosis in patients with metastatic colorectal cancer: a retrospective, exploratory an-alysis of the CORRECT trial. Lancet Oncol 2015; 16: 937-48. https://doi.org/10.1016/S1470-2045(15)00138-2

Murtaza M, Dawson SJ, Tsui DW, Gale D, Forshew T, Piskorz AM, Parkinson C, Chin SF, Kingsbury Z, Wong AS, Marass F, Humphray S, Hadfield J, Bentley D, Chin TM, Brenton JD, Caldas C, Rosenfeld N. Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA. Nature 2013; 497: 108-12. https://doi.org/10.1038/nature12065

Mohamed Suhaimi NA, Foong YM, Lee DY, Phyo WM, Cima I, Lee EX, Goh WL, Lim WY, Chia KS, Kong SL, Gong M, Lim B, Hillmer AM, Koh PK, Ying JY, Tan MH. Non-invasive sensitive detection of KRAS and BRAF mutation in circulating tumor cells of colorectal cancer patients. Mol Oncol 2015; 9: 850-60. https://doi.org/10.1016/j.molonc.2014.12.011

Sanmamed MF, Fernández-Landázuri S, Rodríguez C, Zárate R, Lozano MD, Zubiri L, Perez-Gracia JL, Martín-Algarra S, González A. Quantitative cell-free circulating BRAFV600E mutation analysis by use of droplet digital PCR in the follow-up of patients with melanoma being treated with BRAF inhibitors. Clin Chem 2015; 61: 297-304. https://doi.org/10.1373/clinchem.2014.230235

Roschewski M, Dunleavy K, Pittaluga S, Moorhead M, Pepin F, Kong K, Shovlin M, Jaffe ES, Staudt LM, Lai C, Steinberg SM, Chen CC, Zheng J, Willis TD, Faham M, Wilson WH. Circulating tumour DNA and CT monitoring in patients with untreated diffuse large B-cell lymphoma: a correlative biomarker study. Lancet Oncol 2015; 16: 541-9. https://doi.org/10.1016/S1470-2045(15)70106-3

Forbes SA, Beare D, Gunasekaran P, Leung K, Bindal N, Boutselakis H, Ding M, Bamford S, Cole C, Ward S, Kok CY, Jia M, De T, Teague JW, Stratton MR, McDermott U, Campbell PJ. COSMIC: exploring the world’s knowledge of somatic mutations in human cancer. Nucleic Acids Res 2015; 43: D805-11. https://doi.org/10.1093/nar/gku1075

Shah SP, Köbel M, Senz J, Morin RD, Clarke BA, Wiegand KC, Leung G, Zayed A, Mehl E, Kalloger SE, Sun M, Giuliany R, Yorida E, Jones S, Varhol R, Swenerton KD, Miller D, Clement PB, Crane C, Madore J, Provencher D, Leung P, DeFazio A, Khattra J, Turashvili G, Zhao Y, Zeng T, Glover JN, Vanderhyden B, Zhao C, Parkinson CA, Jimenez-Linan M, Bowtell DD, Mes-Masson AM, Brenton JD, Aparicio SA, Boyd N, Hirst M, Gilks CB, Marra M, Huntsman DG. Mutation of FOXL2 in granulosa-cell tumors of the ovary. N Engl J Med 2009; 360: 2719-29. https://doi.org/10.1056/NEJMoa0902542

Schirripa M, Cremolini C, Loupakis F, Morvillo M, Bergamo F, Zoratto F, Salvatore L, Antoniotti C, Marmorino F, Sensi E, Lupi C, Fontanini G, De Gregorio V, Giannini R, Basolo F, Masi G, Falcone A. Role of NRAS mutations as prognostic and predictive markers in metastatic colorectal cancer. Int J Cancer 2015; 136: 83-90. https://doi.org/10.1002/ijc.28955

Janku F, Lee JJ, Tsimberidou AM, Hong DS, Naing A, Falchook GS, Fu S, Luthra R, Garrido-Laguna I, Kurzrock R. PIK3CA mutations frequently coexist with RAS and BRAF mutations in patients with advanced cancers. PLoS One 2011; 6: e22769. https://doi.org/10.1371/journal.pone.0022769

Kalfa N, Lumbroso S, Boulle N, Guiter J, Soustelle L, Costa P, Chapuis H, Baldet P, Sultan C. Activating mutations of Gsalpha in kidney cancer. J Urol 2006; 176: 891-5. https://doi.org/10.1016/j.juro.2006.04.023

Fecteau RE, Lutterbaugh J, Markowitz SD, Willis J, Guda K. GNAS mutations identify a set of right-sided, RAS mutant, villous colon cancers. PLoS One 2014; 9: e87966. https://doi.org/10.1371/journal.pone.0087966

Sparks AB, Morin PJ, Vogelstein B, Kinzler KW. Mutational analysis of the APC/beta-catenin/Tcf pathway in colorectal cancer. Cancer Res 1998; 58: 1130-4. PMID: 9515795.

National Comprehensive Cancer Network US. NCCN Clinical Practice Guidelines in Oncology, https://www.nccn.org/ professionals/physician_gls/default.aspx; 2020

Van Cutsem E, Cervantes A, Nordlinger B, Arnold D; ESMO Guidelines Working Group. Metastatic colorectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2014; 25 Suppl 3: iii1-9. https://doi.org/10.1093/annonc/mdu260

Lazzari C. Liquid biopsy for lung cancer. Ultraspecialisti, Milan, https://www.tumorealpolmone.it/diagnosi/biopsia-liquida; 2017

Zhu C, Zhuang W, Chen L, Yang W, Ou WB. Frontiers of ctDNA, targeted therapies, and immunotherapy in non-small-cell lung cancer. Transl Lung Cancer Res 2020; 9: 111-38. https://doi.org/10.21037/tlcr.2020.01.09

Passiglia F, Pilotto S, Facchinetti F, Bertolaccini L, Del Re M, Ferrara R, Franchina T, Malapelle U, Menis J, Passaro A, Ramella S, Rossi G, Trisolini R, Novello S. Treatment of advanced non-small-cell lung cancer: The 2019 AIOM (Italian Association of Medical Oncology) clinical practice guidelines. Crit Rev Oncol Hematol 2020; 146: 102858. https://doi.org/10.1016/j.critrevonc.2019.102858

Thress KS, Jacobs V, Angell HK, Yang JC, Sequist LV, Blackhall F, Su WC, Schuler M, Wolf J, Gold KA, Cantarini M, Barrett JC, Jänne PA. Modulation of Biomarker Expression by Osimertinib: Results of the Paired Tumor Biopsy Cohorts of the AURA Phase I Trial. J Thorac Oncol 2017; 12: 1588-94. https://doi.org/10.1016/j.jtho.2017.07.011

Orzes E. Non-small cell lung cancer, liquid biopsy for better treatment. Rare Diseases Observatory, Rome, https://www.osservatoriomalattierare.it/i-tumori-rari/altri-tumori-rari/14769-carcinoma-polmonare-non-a-piccole-cellule-la-biopsia-liquida-per-un-migliore-trattamento; 2019

Abbosh C, Birkbak NJ, Wilson GA, Jamal-Hanjani M, Constantin T, Salari R, Le Quesne J, Moore DA, Veeriah S, Rosenthal R, Marafioti T, Kirkizlar E, Watkins TBK, McGranahan N, Ward S, Martinson L, Riley J, Fraioli F, Al Bakir M, Grönroos E, Zambrana F, Endozo R, Bi WL, Fennessy FM, Sponer N, Johnson D, Laycock J, Shafi S, Czyzewska-Khan J, Rowan A, Chambers T, Matthews N, Turajlic S, Hiley C, Lee SM, Forster MD, Ahmad T, Falzon M, Borg E, Lawrence D, Hayward M, Kolvekar S, Panagiotopoulos N, Janes SM, Thakrar R, Ahmed A, Blackhall F, Summers Y, Hafez D, Naik A, Ganguly A, Kareht S, Shah R, Joseph L, Marie Quinn A, Crosbie PA, Naidu B, Middleton G, Langman G, Trotter S, Nicolson M, Remmen H, Kerr K, Chetty M, Gomersall L, Fennell DA, Nakas A, Rathinam S, Anand G, Khan S, Russell P, Ezhil V, Ismail B, Irvin-Sellers M, Prakash V, Lester JF, Kornaszewska M, Attanoos R, Adams H, Davies H, Oukrif D, Akarca AU, Hartley JA, Lowe HL, Lock S, Iles N, Bell H, Ngai Y, Elgar G, Szallasi Z, Schwarz RF, Herrero J, Stewart A, Quezada SA, Peggs KS, Van Loo P, Dive C, Lin CJ, Rabinowitz M, Aerts HJWL, Hackshaw A, Shaw JA, Zimmermann BG; TRACERx consortium; PEACE consortium, Swanton C. Phylogenetic ctDNA analysis depicts early stage lung cancer evolution. Nature 2017; 545: 446-51. https://doi.org/10.1038/nature22364

Chaudhuri AA, Chabon JJ, Lovejoy AF, Newman AM, Stehr H, Azad TD, Khodadoust MS, Esfahani MS, Liu CL, Zhou L, Scherer F, Kurtz DM, Say C, Carter JN, Merriott DJ, Dudley JC, Binkley MS, Modlin L, Padda SK, Gensheimer MF, West RB, Shrager JB, Neal JW, Wakelee HA, Loo BW Jr, Alizadeh AA, Diehn M. Early Detection of Molecular Residual Disease in Localized Lung Cancer by Circulating Tumor DNA Profiling. Cancer Discov 2017; 7: 1394-403. https://doi.org/10.1158/2159-8290.CD-17-0716

Karlovich C, Goldman JW, Sun JM, Mann E, Sequist LV, Konopa K, Wen W, Angenendt P, Horn L, Spigel D, Soria JC, Solomon B, Camidge DR, Gadgeel S, Paweletz C, Wu L, Chien S, O'Donnell P, Matheny S, Despain D, Rolfe L, Raponi M, Allen AR, Park K, Wakelee H. Assessment of EGFR Mutation Status in Matched Plasma and Tumor Tissue of NSCLC Patients from a Phase I Study of Rociletinib (CO-1686). Clin Cancer Res 2016; 22: 2386-95. https://doi.org/10.1158/1078-0432.CCR-15-1260

Luo J, Shen L, Zheng D. Diagnostic value of circulating free DNA for the detection of EGFR mutation status in NSCLC: a systematic review and meta-analysis. Sci Rep 2014; 4: 6269. https://doi.org/10.1038/srep06269

Normanno N, Denis MG, Thress KS, Ratcliffe M, Reck M. Guide to detecting epidermal growth factor receptor (EGFR) mutations in ctDNA of patients with advanced nonsmall-cell lung cancer. Oncotarget 2017; 8: 12501-16. https://doi.org/10.18632/oncotarget.13915

Novello S, Barlesi F, Califano R, Cufer T, Ekman S, Levra MG, Kerr K, Popat S, Reck M, Senan S, Simo GV, Vansteenkiste J, Peters S; ESMO Guidelines Committee. Metastatic non-small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2016; 27: v1-v27. https://doi.org/10.1093/annonc/mdw326

Oxnard GR, Thress KS, Alden RS, Lawrance R, Paweletz CP, Cantarini M, Yang JC, Barrett JC, Jänne PA. Association Between Plasma Genotyping and Outcomes of Treatment With Osimertinib (AzD9291) in Advanced Non-Small-Cell Lung Cancer. J Clin Oncol 2016; 34: 3375-82. https://doi.org/10.1200/JCO.2016.66.7162

Qiu M, Wang J, Xu Y, Ding X, Li M, Jiang F, Xu L, Yin R. Circulating tumor DNA is effective for the detection of EGFR mutation in non-small cell lung cancer: a meta-analysis. Cancer Epidemiol Biomarkers Prev 2015; 24: 206-12. https://doi.org/10.1158/1055-9965.EPI-14-0895

Rosell R, Moran T, Queralt C, Porta R, Cardenal F, Camps C, Majem M, Lopez-Vivanco G, Isla D, Provencio M, Insa A, Massuti B, Gonzalez-Larriba JL, Paz-Ares L, Bover I, Garcia-Campelo R, Moreno MA, Catot S, Rolfo C, Reguart N, Palmero R, Sánchez JM, Bastus R, Mayo C, Bertran-Alamillo J, Molina MA, Sanchez JJ, Taron M; Spanish Lung Cancer Group. Screening for epidermal growth factor receptor mutations in lung cancer. N Engl J Med 2009; 361: 958-67. https://doi.org/10.1056/NEJMoa0904554

Sacher AG, Paweletz C, Dahlberg SE, Alden RS, O'Connell A, Feeney N, Mach SL, Jänne PA, Oxnard GR. Prospective Validation of Rapid Plasma Genotyping for the Detection of EGFR and KRAS Mutations in Advanced Lung Cancer. JAMA Oncol 2016; 2: 1014-22. https://doi.org/10.1001/jamaoncol.2016.0173

Thress KS, Brant R, Carr TH, Dearden S, Jenkins S, Brown H, Hammett T, Cantarini M, Barrett JC. EGFR mutation detection in ctDNA from NSCLC patient plasma: A cross-platform comparison of leading technologies to support the clinical development of AzD9291. Lung Cancer 2015; 90: 509-15. https://doi.org/10.1016/j.lungcan.2015.10.004

Thompson JC, Yee SS, Troxel AB, Savitch SL, Fan R, Balli D, Lieberman DB, Morrissette JD, Evans TL, Bauml J, Aggarwal C, Kosteva JA, Alley E, Ciunci C, Cohen RB, Bagley S, Stonehouse-Lee S, Sherry VE, Gilbert E, Langer C, Vachani A, Carpenter EL. Detection of Therapeutically Targetable Driver and Resistance Mutations in Lung Cancer Patients by Next-Generation Sequencing of Cell-Free Circulating Tumor DNA. Clin Cancer Res 2016; 22: 5772-82. https://doi.org/10.1158/1078-0432.CCR-16-1231

Zhu G, Ye X, Dong Z, Lu YC, Sun Y, Liu Y, McCormack R, Gu Y, Liu X. Highly sensitive droplet digital PCR method for detection of EGFR-activating mutations in plasma cell-free DNA from patients with advanced non-small cell lung cancer. J Mol Diagn 2015; 17: 265-72. https://doi.org/10.1016/j.jmoldx.2015.01.004

Bettegowda C, Sausen M, Leary RJ, Kinde I, Wang Y, Agrawal N, Bartlett BR, Wang H, Luber B, Alani RM, Antonarakis ES, Azad NS, Bardelli A, Brem H, Cameron JL, Lee CC, Fecher LA, Gallia GL, Gibbs P, Le D, Giuntoli RL, Goggins M, Hogarty MD, Holdhoff M, Hong SM, Jiao Y, Juhl HH, Kim JJ, Siravegna G, Laheru DA, Lauricella C, Lim M, Lipson EJ, Marie SK, Netto GJ, Oliner KS, Olivi A, Olsson L, Riggins GJ, Sartore-Bianchi A, Schmidt K, Shih lM, Oba-Shinjo SM, Siena S, Theodorescu D, Tie J, Harkins TT, Veronese S, Wang TL, Weingart JD, Wolfgang CL, Wood LD, Xing D, Hruban RH, Wu J, Allen PJ, Schmidt CM, Choti MA, Velculescu VE, Kinzler KW, Vogelstein B, Papadopoulos N, Diaz LA Jr. Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci Transl Med 2014; 6: 224ra24. https://doi.org/10.1126/scitranslmed.3007094

Perrone F, Lampis A, Bertan C, Verderio P, Ciniselli CM, Pizzamiglio S, Frattini M, Nucifora M, Molinari F, Gallino G, Gariboldi M, Meroni E, Leo E, Pierotti MA, Pilotti S. Circulating free DNA in a screening program for early colorectal cancer detection. Tumori 2014; 100: 115-21. https://doi.org/10.1700/1491.16389

Siravegna G, Mussolin B, Buscarino M, Corti G, Cassingena A, Crisafulli G, Ponzetti A, Cremolini C, Amatu A, Lauricella C, Lamba S, Hobor S, Avallone A, Valtorta E, Rospo G, Medico E, Motta V, Antoniotti C, Tatangelo F, Bellosillo B, Veronese S, Budillon A, Montagut C, Racca P, Marsoni S, Falcone A, Corcoran RB, Di Nicolantonio F, Loupakis F, Siena S, Sartore-Bianchi A, Bardelli A. Clonal evolution and resistance to EGFR blockade in the blood of colorectal cancer patients. Nat Med 2015; 21: 795-801. https://doi.org/10.1038/nm.3870

Siravegna G, Bardelli A. Blood circulating tumor DNA for non-invasive genotyping of colon cancer patients. Mol. Oncol 2016; 10: 475-80.

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2020-01-11

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Ciro Comparetto, & Franco Borruto. (2020). Liquid Biopsy: A New, Non-Invasive Early Diagnostic and Prognostic Tool in Oncology . Journal of Cancer Research Updates, 9(1), 37–68. https://doi.org/10.30683/1929-2279.2020.09.06

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