Skip to main content
SpringerLink
Log in

Cell-Free DNA in the Liquid Biopsy Context: Role and Differences Between ctDNA and CTC Marker in Cancer Management

  • Protocol
  • First Online:
Cell-free DNA as Diagnostic Markers

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1909))

Abstract

Liquid biopsy is a new diagnostic concept to investigate the molecular features of solid tumors by blood, saliva, urine, and any other body fluids which show a source of potential biomarkers. In cancer patients, it is a simple and less invasive mean, representing a sustainable alternative to interrogate all tumor cells longitudinally, quantifying and characterizing the biological materials (DNAs, RNAs, proteins) which originate from cancer tissues. Circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) analysis from a simple blood draw received enormous attention for the related clinical research results. A rich scientific literature demonstrates that liquid biopsy is a valid instrument to assess the tumor biomarkers in real time and profile the cancer genotype in diagnostic and prognostic field, as well to quantify minimal residual disease, during patient follow-up. This could be a breakthrough for a companion diagnostic and personalized medicine. Liquid biopsy needs further implementation in the methodological aspects as well as cost-based assessment. The number of new molecular diagnostic assays increases day by day, but the standards for their adoption and clinical validation are still to be achieved.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 139.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 179.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Bardelli A, Pantel K (2017) Liquid biopsies, what we do not know (yet). Cancer Cell 31:172–179. https://doi.org/10.1016/j.ccell.2017.01.002

    Article  CAS  PubMed  Google Scholar 

  2. Zhang C, Guan Y, Sun Y et al (2016) Tumor heterogeneity and circulating tumor cells. Cancer Lett 374:216–223. https://doi.org/10.1016/j.canlet.2016.02.024

    Article  CAS  PubMed  Google Scholar 

  3. Hayes DF, Paoletti C (2013) Circulating tumour cells: insights into tumour heterogeneity. J Intern Med 274:137–143

    Article  CAS  PubMed  Google Scholar 

  4. Jamal-Hanjani M, Quezada SA, Larkin J, Swanton C (2015) Translational implications of tumor heterogeneity. Clin Cancer Res 21:1258–1266. https://doi.org/10.1158/1078-0432.CCR-14-1429

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Alix-Panabières C, Pantel K (2016) Clinical applications of circulating tumor cells and circulating tumor DNA as liquid biopsy. Cancer Discov 6:479–491. https://doi.org/10.1158/2159-8290.CD-15-1483

    Article  CAS  PubMed  Google Scholar 

  6. Castro-Giner F, Gkountela S, Donato C et al (2018) Cancer diagnosis using a liquid biopsy: challenges and expectations. Diagnostics 8:31. https://doi.org/10.3390/diagnostics8020031

    Article  PubMed Central  Google Scholar 

  7. Pantel K, Alix-Panabières C (2013) Real-time liquid biopsy in cancer patients: fact or fiction? Cancer Res 73:6384–6388. https://doi.org/10.1158/0008-5472.CAN-13-2030

    Article  CAS  PubMed  Google Scholar 

  8. Han X, Wang J, Sun Y (2017) Circulating tumor DNA as biomarkers for cancer detection. Genomics Proteomics Bioinformatics 15:59–72. https://doi.org/10.1016/j.gpb.2016.12.004

    Article  PubMed  PubMed Central  Google Scholar 

  9. Mandel P, Metais P (1948) Les acides nucléiques du plasma sanguin chez l’homme. C R Seances Soc Biol Fil 142:241–243

    CAS  PubMed  Google Scholar 

  10. Elshimali YI, Khaddour H, Sarkissyan M et al (2013) The clinical utilization of circulating cell free DNA (CCFDNA) in blood of cancer patients. Int J Mol Sci 14:18925–18958. https://doi.org/10.3390/ijms140918925

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Jahr S, Hentze H, Englisch S et al (2001) DNA fragments in the blood plasma of cancer patients: quantitations and evidence for their origin from apoptotic and necrotic cells DNA fragments in the blood plasma of cancer patients: quantitations and evidence for their origin from apoptotic and necrotic cells. Cancer Res 61:1659–1665. https://doi.org/10.1016/0022-1759(75)90106-4

    Article  CAS  PubMed  Google Scholar 

  12. Siravegna G, Marsoni S, Siena S, Bardelli A (2017) Integrating liquid biopsies into the management of cancer. Nat Rev Clin Oncol 14:531–548. https://doi.org/10.1038/nrclinonc.2017.14

    Article  CAS  PubMed  Google Scholar 

  13. Van Dessel LF, Beije N, Helmijr JCA et al (2017) Application of circulating tumor DNA in prospective clinical oncology trials—standardization of preanalytical conditions. Mol Oncol 11:295–304. https://doi.org/10.1002/1878-0261.12037

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Leung F, Kulasingam V, Diamandis EP et al (2016) Circulating tumor DNA as a cancer biomarker: fact or fiction? Clin Chem 62:1054–1060. https://doi.org/10.1373/clinchem.2016.260331

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Moati E, Taly V, Didelot A et al (2018) Role of circulating tumor DNA in the management of patients with colorectal cancer. Clin Res Hepatol Gastroenterol. https://doi.org/10.1016/j.clinre.2018.03.002

    Article  CAS  PubMed  Google Scholar 

  16. Wan JCM, Massie C, Garcia-Corbacho J et al (2017) Liquid biopsies come of age: towards implementation of circulating tumour DNA. Nat Rev Cancer 17:223–238. https://doi.org/10.1038/nrc.2017.7

    Article  CAS  PubMed  Google Scholar 

  17. Norton SE, Luna KK, Lechner JM et al (2013) A new blood collection device minimizes cellular DNA release during sample storage and shipping when compared to a standard device. J Clin Lab Anal 27:305–311. https://doi.org/10.1002/jcla.21603

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Diaz LA, Bardelli A (2014) Liquid biopsies: genotyping circulating tumor DNA. J Clin Oncol 32:579–586. https://doi.org/10.1200/JCO.2012.45.2011

    Article  PubMed  PubMed Central  Google Scholar 

  19. Merker JD, Oxnard GR, Compton C et al (2018) Circulating tumor DNA analysis in patients with cancer: American Society of Clinical Oncology and College of American Pathologists Joint Review. J Clin Oncol 36:1631–1641. https://doi.org/10.1200/JCO.2017.76.8671

    Article  PubMed  Google Scholar 

  20. Ashworth TR (1989) A case of cancer in which cells similar to those in the tumors were seen in the blood after death. Aust Med J 14:146–147

    Google Scholar 

  21. Paget S (1989) The distribution of secondary growths in cancer of the breast. 1889. Cancer Metastasis Rev 8:98–101

    CAS  PubMed  Google Scholar 

  22. Zheng H-C (2017) The molecular mechanisms of chemoresistance in cancers. Oncotarget 8:59950–59964. https://doi.org/10.18632/oncotarget.19048

    Article  PubMed  PubMed Central  Google Scholar 

  23. Gerlinger M, Rowan A, Horswell S. et al (2016) Europe PMC Funders Group intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med 366:883–892. https://doi.org/10.1056/NEJMoa1113205.Intratumor

  24. Maltoni R, Gallerani G, Fici P et al (2016) CTCs in early breast cancer: a path worth taking. Cancer Lett 376:205–210. https://doi.org/10.1016/j.canlet.2016.03.051

    Article  CAS  PubMed  Google Scholar 

  25. Barriere G, Fici P, Gallerani G et al (2014) Circulating tumor cells and epithelial, mesenchymal and stemness markers: characterization of cell subpopulations. Ann Transl Med 2:109. https://doi.org/10.3978/j.issn.2305-5839.2014.10.04

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Andree KC, van Dalum G, Terstappen LWMM (2016) Challenges in circulating tumor cell detection by the CellSearch system. Mol Oncol 10:395–407. https://doi.org/10.1016/j.molonc.2015.12.002

    Article  CAS  PubMed  Google Scholar 

  27. Lalmahomed ZS, Kraan J, Gratama JW et al (2010) Circulating tumor cells and sample size: the more, the better. J Clin Oncol 28:288–289. https://doi.org/10.1200/JCO.2010.28.2764

    Article  Google Scholar 

  28. Kowalik A, Kowalewska M, Góźdź S (2017) Current approaches for avoiding the limitations of circulating tumor cells detection methods—implications for diagnosis and treatment of patients with solid tumors. Transl Res 185:58–84.e15. https://doi.org/10.1016/j.trsl.2017.04.002

    Article  CAS  PubMed  Google Scholar 

  29. Hsieh JC-H, Wu TM-H (2016) The selection strategy for circulating tumor cells (CTCs) isolation and enumeration: technical features, methods, and clinical applications. In: Tumor Metastasis. InTech

    Google Scholar 

  30. Ferreira MM, Ramani VC, Jeffrey SS (2016) Circulating tumor cell technologies. Mol Oncol 10:374–394. https://doi.org/10.1016/j.molonc.2016.01.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Edge SB, Compton CC (2010) The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol 17:1471–1474. https://doi.org/10.1245/s10434-010-0985-4

    Article  PubMed  Google Scholar 

  32. Allard WJ, Matera J, Miller MC et al (2004) Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases. Clin Cancer Res 10:6897–6904. https://doi.org/10.1158/1078-0432.CCR-04-0378

    Article  PubMed  Google Scholar 

  33. Cristofanilli M, Budd GT, Ellis MJ et al (2004) Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med 351:781–791. https://doi.org/10.1056/NEJMoa040766

    Article  CAS  PubMed  Google Scholar 

  34. Lucci A, Hall CS, Lodhi AK et al (2012) Circulating tumour cells in non-metastatic breast cancer: a prospective study. Lancet Oncol 13:688–695. https://doi.org/10.1016/S1470-2045(12)70209-7

    Article  PubMed  Google Scholar 

  35. Müller V, Riethdorf S, Rack B et al (2012) Prognostic impact of circulating tumor cells assessed with the CellSearch System™ and AdnaTest Breast™ in metastatic breast cancer patients: the DETECT study. Breast Cancer Res 14:R118. https://doi.org/10.1186/bcr3243

    Article  PubMed  PubMed Central  Google Scholar 

  36. Kallergi G, Politaki E, Alkahtani S et al (2016) Evaluation of isolation methods for circulating tumor cells (CTCs). Cell Physiol Biochem 40:411–419. https://doi.org/10.1159/000452556

    Article  CAS  PubMed  Google Scholar 

  37. Yu M, Bardia A, Wittner BS et al (2013) Circulating breast tumor cells exhibit dynamic changes in epithelial and mesenchymal composition. Science 339:580–584. https://doi.org/10.1126/science.1228522

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Jordan NV, Bardia A, Wittner BS et al (2016) HER2 expression identifies dynamic functional states within circulating breast cancer cells. Nature 537:102–106. https://doi.org/10.1038/nature19328

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Antonarakis ES, Lu C, Wang H et al (2014) AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer. N Engl J Med 371:1028–1038. https://doi.org/10.1056/NEJMoa1315815

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Paoletti C, Muñiz MC, Thomas DG et al (2015) Development of circulating tumor cell-endocrine therapy index in patients with hormone receptor-positive breast cancer. Clin Cancer Res 21:2487–2498. https://doi.org/10.1158/1078-0432.CCR-14-1913

    Article  CAS  PubMed  Google Scholar 

  41. Carter L, Rothwell DG, Mesquita B et al (2017) Molecular analysis of circulating tumor cells identifies distinct copy-number profiles in patients with chemosensitive and chemorefractory small-cell lung cancer. Nat Med 23:114–119. https://doi.org/10.1038/nm.4239

    Article  CAS  PubMed  Google Scholar 

  42. Mazel M, Jacot W, Pantel K et al (2015) Frequent expression of PD-L1 on circulating breast cancer cells. Mol Oncol 9:1773–1782. https://doi.org/10.1016/j.molonc.2015.05.009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Hong X, Sullivan RJ, Kalinich M et al (2018) Molecular signatures of circulating melanoma cells for monitoring early response to immune checkpoint therapy. Proc Natl Acad Sci 115:2467–2472. https://doi.org/10.1073/pnas.1719264115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Yu M, Bardia A, Aceto N et al (2014) Ex vivo culture of circulating breast tumor cells for individualized testing of drug susceptibility. Science 345:216–220. https://doi.org/10.1126/science.1253533

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Gao D, Vela I, Sboner A et al (2014) Organoid cultures derived from patients with advanced prostate cancer. Cell 159:176–187. https://doi.org/10.1016/j.cell.2014.08.016.Organoid

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Cayrefourcq L, Mazard T, Joosse S et al (2015) Establishment and characterization of a cell line from human circulating colon cancer cells. Cancer Res 75:892–901. https://doi.org/10.1158/0008-5472.CAN-14-2613

    Article  CAS  PubMed  Google Scholar 

  47. Lallo A, Schenk MW, Frese KK et al (2017) Circulating tumor cells and CDX models as a tool for preclinical drug development. Transl Lung Cancer Res 6:397–408. https://doi.org/10.21037/tlcr.2017.08.01

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Ilie M, Hofman V, Long-Mira E et al (2014) “Sentinel” circulating tumor cells allow early diagnosis of lung cancer in patients with chronic obstructive pulmonary disease. PLoS One 9:4–10. https://doi.org/10.1371/journal.pone.0111597

    Article  CAS  Google Scholar 

  49. Wan JCM, Massie C, Garcia-Corbacho J et al (2016) Liquid biopsies come of age: clinical applications of circulating tumour DNA. Nat Rev Cancer 17:223–238. https://doi.org/10.1038/nrc.2017.7

    Article  CAS  Google Scholar 

  50. Kamat AA, Bischoff FZ, Dang D et al (2006) Circulating cell-free DNA: a novel biomarker for response to therapy in ovarian carcinoma. Cancer Biol Ther 5:1369–1374. https://doi.org/10.4161/cbt.5.10.3240

    Article  CAS  PubMed  Google Scholar 

  51. Bettegowda C, Sausen M, Leary R et al (2014) Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci Transl Med 6:224ra24. https://doi.org/10.1126/scitranslmed.3007094.Detection

    Article  PubMed  PubMed Central  Google Scholar 

  52. Gautschi O, Huegli B, Ziegler A et al (2007) Origin and prognostic value of circulating KRAS mutations in lung cancer patients. Cancer Lett 254:265–273. https://doi.org/10.1016/j.canlet.2007.03.008

    Article  CAS  PubMed  Google Scholar 

  53. Wang S, An T, Wang J et al (2010) Potential clinical significance of a plasma-based KRAS mutation analysis in patients with advanced non-small cell lung cancer. Clin Cancer Res 16:1324–1330. https://doi.org/10.1158/1078-0432.CCR-09-2672

    Article  CAS  PubMed  Google Scholar 

  54. Scherer F, Kurtz DM, Newman AM et al (2016) Distinct biological subtypes and patterns of genome evolution in lymphoma revealed by circulating tumor DNA. Sci Transl Med 8:364ra155. https://doi.org/10.1126/scitranslmed.aai8545

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Newman AM, Bratman SV, To J et al (2014) An ultrasensitive method for quantitating circulating tumor DNA with broad patient coverage. Nat Med 20:548–554. https://doi.org/10.1038/nm.3519

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Beaver JA, Jelovac D, Balukrishna S et al (2014) Detection of cancer DNA in plasma of patients with early-stage breast cancer. Clin Cancer Res 20:2643–2650. https://doi.org/10.1158/1078-0432.CCR-13-2933

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Thierry AR, Mouliere F, El Messaoudi S et al (2014) Clinical validation of the detection of KRAS and BRAF mutations from circulating tumor DNA. Nat Med 20:430–435. https://doi.org/10.1038/nm.3511

    Article  CAS  PubMed  Google Scholar 

  58. Bachet JB, Bouché O, Taieb J et al (2018) RAS mutation analysis in circulating tumor DNA from patients with metastatic colorectal cancer: the AGEO RASANC prospective multicenter study. Ann Oncol 29:1211–1219. https://doi.org/10.1093/annonc/mdy061

    Article  CAS  PubMed  Google Scholar 

  59. Cohen PA, Flowers N, Tong S et al (2016) Abnormal plasma DNA profiles in early ovarian cancer using a non-invasive prenatal testing platform: implications for cancer screening. BMC Med 14:10–15. https://doi.org/10.1186/s12916-016-0667-6

    Article  Google Scholar 

  60. Mao L, Hruban RH, Boyle JO et al (1994) Detection of oncogene mutations in sputum precedes diagnosis of lung cancer advances in brief detection of oncogene mutations in sputum precedes diagnosis of lung cancer. Cancer 54:1634–1637

    CAS  Google Scholar 

  61. Gormally E, Vineis P, Matullo G et al (2006) TP53 and KRAS2 mutations in plasma DNA of healthy subjects and subsequent cancer occurrence: a prospective study. Cancer Res 66:6871–6876. https://doi.org/10.1158/0008-5472.CAN-05-4556

    Article  CAS  PubMed  Google Scholar 

  62. Birkenkamp-Demtröder K, Nordentoft I, Christensen E et al (2016) Genomic alterations in liquid biopsies from patients with bladder cancer. Eur Urol 70:75–82. https://doi.org/10.1016/j.eururo.2016.01.007

    Article  CAS  PubMed  Google Scholar 

  63. Sidransky D, Tokino T, Hamilton SR et al (1992) Identification of ras oncogene mutations in the stool of patients with curable colorectal tumors. Science 256:102–105

    Article  CAS  PubMed  Google Scholar 

  64. Nair N, Camacho-Vanegas O, Rykunov D et al (2016) Genomic analysis of uterine lavage fluid detects early endometrial cancers and reveals a prevalent landscape of driver mutations in women without histopathologic evidence of cancer: a prospective cross-sectional study. PLoS Med 13:e1002206. https://doi.org/10.1371/journal.pmed.1002206

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Ross-Innes CS, Chettouh H, Achilleos A et al (2017) Risk stratification of Barrett’s oesophagus using a non-endoscopic sampling method coupled with a biomarker panel: a cohort study. Lancet Gastroenterol Hepatol 2:23–31. https://doi.org/10.1016/S2468-1253(16)30118-2

    Article  PubMed  Google Scholar 

  66. Chan KCA, Hung ECW, Woo JKS et al (2013) Early detection of nasopharyngeal carcinoma by plasma Epstein-Barr virus DNA analysis in a surveillance program. Cancer 119:1838–1844. https://doi.org/10.1002/cncr.28001

    Article  CAS  PubMed  Google Scholar 

  67. Guerrero-Preston R, Valle BL, Jedlicka A et al (2016) Molecular triage of premalignant lesions in liquid-based cervical cytology and circulating cell-free DNA from urine, using a panel of methylated human papilloma virus and host genes. Cancer Prev Res 9:915–924. https://doi.org/10.1158/1940-6207.CAPR-16-0138

    Article  CAS  Google Scholar 

  68. Tie J, Semira C, Gibbs P (2018) Circulating tumor DNA as a biomarker to guide therapy in post-operative locally advanced rectal cancer: the best option? Expert Rev Mol Diagn 18:1–3. https://doi.org/10.1080/14737159.2018.1386558

    Article  CAS  PubMed  Google Scholar 

  69. Tie J, Wang Y, Tomasetti C et al (2016) Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer. Sci Transl Med 8:346ra92. https://doi.org/10.1126/scitranslmed.aaf6219

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Symonds EL, Pedersen SK, Murray DH et al (2018) Circulating tumour DNA for monitoring colorectal cancer-a prospective cohort study to assess relationship to tissue methylation, cancer characteristics and surgical resection. Clin Epigenetics 10:63. https://doi.org/10.1186/s13148-018-0500-5

    Article  PubMed  PubMed Central  Google Scholar 

  71. De Mattos-Arruda L, Weigelt B, Cortes J et al (2014) Capturing intra-tumor genetic heterogeneity by de novo mutation profiling of circulating cell-free tumor DNA: a proof-of-principle. Ann Oncol 25:1729–1735. https://doi.org/10.1093/annonc/mdu239

    Article  PubMed  PubMed Central  Google Scholar 

  72. Jamal-Hanjani M, Wilson GA, Horswell S et al (2016) Detection of ubiquitous and heterogeneous mutations in cell-free DNA from patients with early-stage non-small-cell lung cancer. Ann Oncol 27:862–867. https://doi.org/10.1093/annonc/mdw037

    Article  CAS  PubMed  Google Scholar 

  73. De Mattos-Arruda L, Bidard FC, Won HH et al (2014) Establishing the origin of metastatic deposits in the setting of multiple primary malignancies: the role of massively parallel sequencing. Mol Oncol 8:150–158. https://doi.org/10.1016/j.molonc.2013.10.006

    Article  CAS  PubMed  Google Scholar 

  74. Murtaza M, Dawson SJ, Pogrebniak K et al (2015) Multifocal clonal evolution characterized using circulating tumour DNA in a case of metastatic breast cancer. Nat Commun 6:1–6. https://doi.org/10.1038/ncomms9760

    Article  CAS  Google Scholar 

  75. Bin KY, Chen JS, Fand CW et al (2014) Comparison of KRAS mutation analysis of primary tumors and matched circulating cell-free DNA in plasmas of patients with colorectal cancer. Clin Chim Acta 433:284–289. https://doi.org/10.1016/j.cca.2014.03.024

    Article  CAS  Google Scholar 

  76. Tie J, Kinde I, Wang Y et al (2015) Circulating tumor DNA as an early marker of therapeutic response in patients with metastatic colorectal cancer. Ann Oncol 26:1715–1722. https://doi.org/10.1093/annonc/mdv177

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Shu Y, Wu X, Tong X et al (2017) Circulating tumor DNA mutation profiling by targeted next generation sequencing provides guidance for personalized treatments in multiple cancer types. Sci Rep 7:1–11. https://doi.org/10.1038/s41598-017-00520-1

    Article  CAS  Google Scholar 

  78. Garlan F, Laurent-Puig P, Sefrioui D et al (2017) Early evaluation of circulating tumor DNA as marker of therapeutic efficacy in metastatic colorectal cancer patients (PLACOL Study). Clin Cancer Res 23:5416–5425. https://doi.org/10.1158/1078-0432.CCR-16-3155

    Article  CAS  PubMed  Google Scholar 

  79. Diaz LA Jr, Williams RT, Wu J et al (2012) The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers. Nature 486:537–540. https://doi.org/10.1038/nature11219

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Kobayashi S, Boggon TJ, Dayaram T et al (2005) EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. N Engl J Med 352:786–792. https://doi.org/10.1056/NEJMoa044238

    Article  CAS  PubMed  Google Scholar 

  81. Chu D, Paoletti C, Gersch C et al (2016) ESR1 mutations in circulating plasma tumor DNA from metastatic breast cancer patients. Clin Cancer Res 22:993–999. https://doi.org/10.1158/1078-0432.CCR-15-0943

    Article  CAS  PubMed  Google Scholar 

  82. Guttery DS, Page K, Hills A et al (2015) Noninvasive detection of activating estrogen receptor 1 (ESR1) mutations in estrogen receptor-positive metastatic breast cancer. Clin Chem 61:974–982. https://doi.org/10.1373/clinchem.2015.238717

    Article  CAS  PubMed  Google Scholar 

  83. Siravegna G, Mussolin B, Buscarino M et al (2015) Clonal evolution and resistance to EGFR blockade in the blood of colorectal cancer patients. Nat Med 21:795–801. https://doi.org/10.1038/nm.3870

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Kidess-Sigal E, Liu HE, Triboulet MM et al (2016) Enumeration and targeted analysis of KRAS, BRAF and PIK3CA mutations in CTCs captured by a label-free platform: comparison to ctDNA and tissue in metastatic colorectal cancer. Oncotarget 7:85349–85364. https://doi.org/10.18632/oncotarget.13350

    Article  PubMed  PubMed Central  Google Scholar 

  85. Che J, Mach AJ, Go DE et al (2013) Microfluidic purification and concentration of malignant pleural effusions for improved molecular and cytomorphological diagnostics. PLoS One 8:e78194. https://doi.org/10.1371/journal.pone.0078194

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Sollier E, Go DE, Che J et al (2014) Size-selective collection of circulating tumor cells using Vortex technology. Lab Chip 14:63–77. https://doi.org/10.1039/c3lc50689d

    Article  CAS  PubMed  Google Scholar 

  87. Che J, Yu V, Dhar M et al (2016) Classification of large circulating tumor cells isolated with ultra-high throughput microfluidic Vortex technology. Oncotarget 7:12748–12760. https://doi.org/10.18632/oncotarget.7220

    Article  PubMed  PubMed Central  Google Scholar 

  88. Kidess E, Heirich K, Wiggin M et al (2015) Mutation profiling of tumor DNA from plasma and tumor tissue of colorectal cancer patients with a novel, high-sensitivity multiplexed mutation detection platform. Oncotarget 6:2549. https://doi.org/10.18632/oncotarget.3041

    Article  PubMed  Google Scholar 

  89. Madic J, Kiialainen A, Bidard F-C et al (2015) Circulating tumor DNA and circulating tumor cells in metastatic triple negative breast cancer patients. Int J Cancer 136:2158–2165. https://doi.org/10.1002/ijc.29265

    Article  CAS  PubMed  Google Scholar 

  90. Sundaresan TK, Sequist LV, Heymach JV et al (2016) Detection of T790M, the acquired resistance EGFR mutation, by tumor biopsy versus noninvasive blood-based analyses. Clin Cancer Res 22:1103–1110. https://doi.org/10.1158/1078-0432.CCR-15-1031

    Article  CAS  PubMed  Google Scholar 

  91. Stott SL, Hsu C-H, Tsukrov DI et al (2010) Isolation of circulating tumor cells using a microvortex-generating herringbone-chip. Proc Natl Acad Sci 107:18392–18397. https://doi.org/10.1073/pnas.1012539107

    Article  PubMed  PubMed Central  Google Scholar 

  92. Chimonidou M, Strati A, Malamos N et al (2017) Direct comparison study of DNA methylation markers in EpCAM-positive circulating tumour cells, corresponding circulating tumour DNA, and paired primary tumours in breast cancer. Oncotarget 8:564–565. https://doi.org/10.18632/oncotarget.18679

    Article  Google Scholar 

  93. Rossi G, Mu Z, Rademaker AW et al (2018) Cell-free DNA and circulating tumor cells: comprehensive liquid biopsy analysis in advanced breast cancer. Clin Cancer Res 24:560–568. https://doi.org/10.1158/1078-0432.CCR-17-2092

    Article  CAS  PubMed  Google Scholar 

  94. Neumann MHD, Bender S, Krahn T, Schlange T (2018) ctDNA and CTCs in liquid biopsy—current status and where we need to progress. Comput Struct Biotechnol J 16:190–195. https://doi.org/10.1016/j.csbj.2018.05.002

    Article  PubMed  PubMed Central  Google Scholar 

  95. Hanssen A, Wagner J, Gorges TM et al (2016) Characterization of different CTC subpopulations in non-small cell lung cancer. Sci Rep 6:28010. https://doi.org/10.1038/srep28010

    Article  PubMed  PubMed Central  Google Scholar 

  96. Sequist LV, Nagrath S, Toner M et al (2009) The CTC-chip: an exciting new tool to detect circulating tumor cells in lung cancer patients. J Thorac Oncol 4:281–283. https://doi.org/10.1097/JTO.0b013e3181989565

    Article  PubMed  PubMed Central  Google Scholar 

  97. Deng G, Herrler M, Burgess D et al (2008) Enrichment with anti-cytokeratin alone or combined with anti-EpCAM antibodies significantly increases the sensitivity for circulating tumor cell detection in metastatic breast cancer patients. Breast Cancer Res 10:1–11. https://doi.org/10.1186/bcr2131

    Article  CAS  Google Scholar 

  98. Yang AD, Fan F, Camp ER et al (2006) Chronic oxaliplatin resistance induces epithelial-to-mesenchymal transition in colorectal cancer cell lines. Clin Cancer Res 12:4147–4153. https://doi.org/10.1158/1078-0432.CCR-06-0038

    Article  CAS  PubMed  Google Scholar 

  99. Gorges TM, Tinhofer I, Drosch M et al (2012) Circulating tumour cells escape from EpCAM-based detection due to epithelial-to-mesenchymal transition. BMC Cancer 12:178

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Alix-Panabières C (2012) EPISPOT assay: detection of viable DTCs/CTCs in solid tumor patients. Recent Results Cancer Res 195:69–76

    Article  PubMed  Google Scholar 

  101. Lin M, Chen J, Lu Y et al (2014) Nanostructure embedded microchips for detection, isolation, and characterization of circulating tumor cells. Acc Chem Res 47:2941–2950. https://doi.org/10.1021/ar5001617

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Awasthi NP, Kumari S, Neyaz A et al (2017) EpCAM-based flow cytometric detection of circulating tumor cells in gallbladder carcinoma cases. Asian Pac J Cancer Prev 18:3429–3437. https://doi.org/10.22034/APJCP.2017.18.12.3429

    Article  PubMed  PubMed Central  Google Scholar 

  103. Hristozova T, Konschak R, Budach V, Tinhofer I (2012) A simple multicolor flow cytometry protocol for detection and molecular characterization of circulating tumor cells in epithelial cancers. Cytometry A 81:489–495. https://doi.org/10.1002/cyto.a.22041

    Article  CAS  PubMed  Google Scholar 

  104. Desitter I, Guerrouahen BS, Benali-Furet N et al (2011) A new device for rapid isolation by size and characterization of rare circulating tumor cells. Anticancer Res 442:427–441

    Google Scholar 

  105. Laget S, Broncy L, Hormigos K et al (2017) Technical insights into highly sensitive isolation and molecular characterization of fixed and live circulating tumor cells for early detection of tumor invasion. PLoS One 12(1):e0169427

    Article  PubMed  PubMed Central  Google Scholar 

  106. Fabbri F, Carloni S, Zoli W et al (2013) Detection and recovery of circulating colon cancer cells using a dielectrophoresis-based device: KRAS mutation status in pure CTCs. Cancer Lett 335:225–231. https://doi.org/10.1016/j.canlet.2013.02.015

    Article  CAS  PubMed  Google Scholar 

  107. Maltoni R, Fici P, Amadori D et al (2015) Circulating tumor cells in early breast cancer: a connection with vascular invasion. Cancer Lett 367:43–48. https://doi.org/10.1016/j.canlet.2015.06.020

    Article  CAS  PubMed  Google Scholar 

  108. Kim MS, Kim J, Lee W et al (2013) A trachea-inspired bifurcated microfilter capturing viable circulating tumor cells via altered biophysical properties as measured by atomic force microscopy. Small 9:3103–3110. https://doi.org/10.1002/smll.201202317

    Article  CAS  PubMed  Google Scholar 

  109. Plouffe BD, Murthy SK, Lewis LH (2015) Fundamentals and application of magnetic particles in cell isolation and enrichment: a review. Rep Prog Phys 78:016601. https://doi.org/10.1088/0034-4885/78/1/016601

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy

    Pietro Fici

Authors
  1. Pietro Fici
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Pietro Fici .

Editor information

Editors and Affiliations

  1. Biosciences Laboratory, IRCCS I.R.S.T, Meldola, Italy

    Valentina Casadio

  2. Biosciences Laboratory, IRCCS I.R.S.T, Meldola, Italy

    Samanta Salvi

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Science+Business Media, LLC, part of Springer Nature

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

Fici, P. (2019). Cell-Free DNA in the Liquid Biopsy Context: Role and Differences Between ctDNA and CTC Marker in Cancer Management. In: Casadio, V., Salvi, S. (eds) Cell-free DNA as Diagnostic Markers. Methods in Molecular Biology, vol 1909. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-8973-7_4

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-8973-7_4

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-8972-0

  • Online ISBN: 978-1-4939-8973-7

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation