Skip to main content

Circulating Tumour Cells in Lung Cancer

  • Chapter
  • First Online:

Part of the book series: Recent Results in Cancer Research ((RECENTCANCER,volume 215))

Abstract

Circulating tumour cells (CTCs) constitute a potential tumour surrogate that could serve as “liquid biopsy” with the advantage to be a minimally invasive approach compared to traditional tissue biopsies. As CTCs are thought to be the source of metastatic lesions, their analysis represents a potential means of tracking cancer cells from the primary tumour en route to distant sites, thus providing valuable insights into the metastatic process. However, several problems, such as their rarity in the peripheral blood, the technical limitations of single-cell downstream analysis and their phenotypic variability, make CTC detection and molecular characterisation very challenging. Nevertheless, in the last decade, there has been an exponential increase of interest in the development of powerful cellular and molecular methodologies applied to CTCs. In this chapter, we focus on the recent advances of functional studies and molecular profiling of CTCs. We will also highlight the clinical relevance of CTC detection and enumeration, and discuss their potential as tumour biomarkers with special focus on lung cancer.

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

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   49.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   64.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   89.99
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

Learn about institutional subscriptions

References

  • Abbosh C, Birkbak NJ, Wilson GA, Jamal-Hanjani M, Constantin T, Salari R et al (2017) Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution. Nature 545(7655)

    Google Scholar 

  • Aceto N, Bardia A, Miyamoto DT, Donaldson MC, Wittner BS, Spencer JA et al (2014) Circulating tumor cell clusters are oligoclonal precursors of breast cancer metastasis. Cell 158(5):1110–1122

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Alix-Panabieres C, Pantel K (2014) Challenges in circulating tumour cell research. Nat Rev Cancer 14(9):623–631

    Article  CAS  PubMed  Google Scholar 

  • Allard WJ, Matera J, Miller MC, Repollet M, Connelly MC, Rao C et al (2005) Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with non. Clin Cancer Res 10(October):6897–6904

    Google Scholar 

  • American Cancer S (2016) Cancer Facts & Figures 2016. Cancer Facts & Fig 2016:1–9

    Google Scholar 

  • Baccelli I, Schneeweiss A, Riethdorf S, Stenzinger A, Schillert A, Vogel V et al (2013) Identification of a population of blood circulating tumor cells from breast cancer patients that initiates metastasis in a xenograft assay. Nat Biotechnol 31(6):539–544

    Article  CAS  PubMed  Google Scholar 

  • Brock MV, Hooker CM, Ota-Machida E, Han Y, Guo M, Ames S et al (2008) DNA methylation markers and early recurrence in stage I lung cancer. N Engl J Med 358(11):1118–1128

    Article  CAS  PubMed  Google Scholar 

  • Carlsson A, Nair VS, Luttgen MS, Keu KV, Horng G, Vasanawala M et al (2014) Circulating tumor microemboli diagnostics for patients with non-small cell lung cancer. J Thorac Oncol: Off Publ Int Assoc Study Lung Cancer. 9(8):1111–1119. PubMed PMID: PMC4145608

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Carter L, Rothwell DG, Mesquita B, Smowton C, Leong HS, Fernandez-Gutierrez F et al (2016) Molecular analysis of circulating tumor cells identifies distinct copy-number profiles in patients with chemosensitive and chemorefractory small-cell lung cancer. Nat Med 23(November)

    Google Scholar 

  • Cayrefourcq L, Mazard T, Joosse S, Solassol J, Ramos J, Assenat E et al (2015) Establishment and characterization of a cell line from human Circulating colon cancer cells. Can Res 75(5):892–901

    Article  CAS  Google Scholar 

  • Chen C-L, Mahalingam D, Osmulski P, Jadhav RR, Wang C-M, Leach RJ et al (2013) Single-cell analysis of circulating tumor cells identifies cumulative expression patterns of EMT-related genes in metastatic prostate cancer. Prostate 73(8):813–826

    Article  PubMed  CAS  Google Scholar 

  • Chimonidou M, Strati A, Malamos N, Kouneli S (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

    Google Scholar 

  • Chudziak J, Burt DJ, Mohan S, Rothwell DG, Mesquita B, Antonello J et al (2016) Clinical evaluation of a novel microfluidic device for epitope-independent enrichment of circulating tumour cells in patients with small cell lung cancer. Analyst 141(2):669–78. PubMed PMID: 26605519. Epub 2015/11/26. eng

    Article  CAS  PubMed  Google Scholar 

  • Cohen SJ, Punt CJA, Iannotti N, Saidman BH, Sabbath KD, Gabrail NY et al (2008) Relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer. J Clin Oncol 26(19):3213–3221

    Article  PubMed  Google Scholar 

  • Cristofanilli M, Budd GT, Ellis MJ, Stopeck A, Matera J, Miller MC et al (2004) Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med 351(8):781–791

    Article  CAS  PubMed  Google Scholar 

  • Crosbie PA, Shah R, Krysiak P, Zhou C, Morris K, Tugwood J et al (2016) Circulating tumor cells detected in the tumor-draining pulmonary vein are associated with disease recurrence after surgical resection of NSCLC. J Thorac Oncol 11(10):1793–1797

    Article  PubMed  PubMed Central  Google Scholar 

  • de Bono JS, Scher HI, Montgomery RB, Parker C, Miller MC, Tissing H et al (2008) Circulating tumor cells predict survival benefit from treatment in metastatic castration-resistant prostate cancer. Clin Cancer Res 14(19):6302–6309

    Article  PubMed  CAS  Google Scholar 

  • de Bruin EC, McGranahan N, Mitter R, Salm M, Wedge DC, Yates L et al (2014) Spatial and temporal diversity in genomic instability processes defines lung cancer evolution. Science 346(6206):251–256

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Dean FB, Hosono S, Fang L, Wu X, Faruqi AF, Bray-Ward P et al (2002) Comprehensive human genome amplification using multiple displacement amplification. Proc Natl Acad Sci 99(8):5261–5266

    Article  CAS  Google Scholar 

  • Dong X, Zhang L, Milholland B, Lee M, Maslov AY, Wang T et al (2017) Accurate identification of single-nucleotide variants in whole-genome-amplified single cells. Nat Methods 20(10)

    Google Scholar 

  • Dorsey JF, Kao GD, Macarthur KM, Ju M, Steinmetz D, Paul E et al (2015) Tracking viable circulating tumor cells (CTCs) in the peripheral blood of non-small cell lung cancer patients undergoing definitive radiation therapy: pilot study results. Cancer 121(1):139–149

    Article  PubMed  Google Scholar 

  • Du Y-J, Li J, Zhu W-F, Wu Y, Tang X-P, Wang Y et al (2014) Survivin mRNA-circulating tumor cells predict treatment efficacy of chemotherapy and survival for advanced non-small cell lung cancer patients. Tumour Biol: J Int Soc Oncodevelopmental Biol Med 35(5):4499–4507

    Article  CAS  Google Scholar 

  • Faugeroux V, Pailler E, Auger N, Taylor M, Farace F (2014) Clinical utility of circulating tumor cells in ALK-positive non-small-cell lung cancer. Front Oncol 4(281)

    Google Scholar 

  • Fiorelli A, Accardo M, Carelli E, Angioletti D, Santini M, Di Domenico M (2015) Circulating tumor cells in diagnosing lung cancer: clinical and morphologic analysis. Ann Thorac Surg 99(6):1899–1905

    Article  PubMed  Google Scholar 

  • Gawad C, Koh W, Quake SR (2016) Single-cell genome sequencing: current state of the science. Nat Rev Genet 17(3):175–188

    Article  CAS  PubMed  Google Scholar 

  • Girotti MR, Gremel G, Lee R, Galvani E, Rothwell D, Viros A et al (2016 ) Application of sequencing, liquid biopsies, and patient-derived xenografts for personalized medicine in melanoma. Cancer Discov 6(3):286–99. PubMed PMID: ISI:000373439500024. English

    Google Scholar 

  • Grillet F, Bayet E, Villeronce O, Zappia L, Lagerqvist EL, Lunke S et al (2017) Circulating tumour cells from patients with colorectal cancer have cancer stem cell hallmarks in ex vivo culture. Gut 66(10):1802–1810

    Article  CAS  PubMed  Google Scholar 

  • He J, Tan W, Ma J (2017) Circulating tumor cells and DNA for real-time EGFR detection and monitoring of non-small-cell lung cancer

    Google Scholar 

  • Heitzer E, Auer M, Gasch C, Pichler M, Ulz P, Hoffmann EM et al (2013) Complex tumor genomes inferred from single circulating tumor cells by array-CGH and next-generation sequencing. Can Res 73(10):2965

    Article  CAS  Google Scholar 

  • Hodgkinson CL, Morrow CJ, Li Y, Metcalf RL, Rothwell DG, Trapani F et al (2014) Tumorigenicity and genetic profiling of circulating tumor cells in small-cell lung cancer. Nat Med 20(8):897–903

    Article  CAS  PubMed  Google Scholar 

  • Hofman V, Bonnetaud C Fau-Ilie MI, Ilie Mi Fau-Vielh P, Vielh P Fau-Vignaud JM, Vignaud Jm Fau-Flejou JF, Flejou Jf Fau-Lantuejoul S et al (2011) Preoperative circulating tumor cell detection using the isolation by size of epithelial tumor cell method for patients with lung cancer is a new prognostic biomarker. Clin Cancer Res 20110217 DCOM- 20110815(1078–0432 (Print)). eng

    Google Scholar 

  • Hofman VJ, Ilie M, Hofman PM (2016) Detection and characterization of circulating tumor cells in lung cancer: Why and how? Cancer Cytopathol 124(6):380–387

    Article  PubMed  Google Scholar 

  • Hou JM, Krebs MG, Lancashire L, Sloane R, Backen A, Swain RK et al (2012) Clinical significance and molecular characteristics of circulating tumor cells and circulating tumor microemboli in patients with small-cell lung cancer. J Clin Oncol 30(5):525–532

    Article  PubMed  Google Scholar 

  • Ilie M, Hofman V, Long-Mira E, Selva E, Vignaud JM, Padovani B et al (2014) “Sentinel” circulating tumor cells allow early diagnosis of lung cancer in patients with Chronic obstructive pulmonary disease. PLoS ONE 9(10):4–10

    Article  CAS  Google Scholar 

  • Jamal-hanjani M, Hackshaw A, Ngai Y, Shaw J, Dive C, Quezada S et al (2014) Tracking genomic cancer evolution for precision medicine: the lung TRACERx Study 12(7)

    Google Scholar 

  • Jones PA (2012) Functions of DNA methylation: Islands, start sites, gene bodies and beyond. Nat Rev Genet 13(7):484–492

    Article  CAS  PubMed  Google Scholar 

  • Juan O, Vidal J, Gisbert R, Muñoz J, Maciá S, Gómez-Codina J (2014) Prognostic significance of circulating tumor cells in advanced non-small cell lung cancer patients treated with docetaxel and gemcitabine. Clin Transl Oncol 16(7):637–643

    Article  CAS  PubMed  Google Scholar 

  • Klameth L, Rath B, Hochmaier M, Moser D, Redl M, Mungenast F et al (2017) Small cell lung cancer: model of circulating tumor cell tumorospheres in chemoresistance. Sci Rep 7(1):5337

    Google Scholar 

  • Klein CA, Schmidt-Kittler O, Schardt JA, Pantel K, Speicher MR, Riethmüller G (1999) Comparative genomic hybridization, loss of heterozygosity, and DNA sequence analysis of single cells. Proc Natl Acad Sci 96(8):4494–4499

    Article  CAS  Google Scholar 

  • Klein CA, Seidl S, Petat-Dutter K, Offner S, Geigl JB, Schmidt-Kittler O et al (2002) Combined transcriptome and genome analysis of single micrometastatic cells. Nat Biotech. 20(4):387–392

    Article  CAS  Google Scholar 

  • Kolostova K, Zhang Y, Hoffman RM, Bobek V (2014a) In vitro culture and characterization of human lung cancer circulating tumor cells isolated by size exclusion from an orthotopic nude-mouse model expressing fluorescent protein. J Fluoresc 24(5):1531–1536

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kolostova K, Broul M, Schraml J, Cegan M, Matkowski R, Fiutowski M et al (2014b) Circulating tumor cells in localized prostate cancer: Isolation, cultivation In Vitro and relationship to T-stage and gleason score. Anticancer Res 34(7):3641–3646

    PubMed  Google Scholar 

  • Kowalik A, Kowalewska M, Gozdz 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. PubMed PMID: 28506696. Epub 2017/05/17. eng

    Article  PubMed  CAS  Google Scholar 

  • Krebs MG, Sloane R, Priest L, Lancashire L, Hou JM, Greystoke A et al (2011) Evaluation and prognostic significance of circulating tumor cells in patients with non-small-cell lung cancer. J Clin Oncol 29(12):1556–1563

    Article  PubMed  Google Scholar 

  • Krebs MG, Hou JM, Sloane R, Lancashire L, Priest L, Nonaka D et al (2012) Analysis of circulating tumor cells in patients with non-small cell lung cancer using epithelial marker-dependent and -independent approaches. J Thorac Oncol 7(2):306–315

    Article  PubMed  Google Scholar 

  • Lallo A, Schenk MW, Frese KK, Blackhall F, Dive C (2017) Circulating tumor cells and CDX models as a tool for preclinical drug development. Transl Lung Cancer Res 6(4):397–408

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Larson CJ, Moreno JG, Pienta KJ, Gross S, Repollet M, O’Hara SM et al (2004) Apoptosis of circulating tumor cells in prostate cancer patients. Cytometry Part A. 62(1):46–53

    Article  Google Scholar 

  • Lee CK, Brown C, Gralla RJ, Hirsh V, Thongprasert S, Tsai CM et al (2013) Impact of EGFR inhibitor in non-small cell lung cancer on progression-free and overall survival: a meta-analysis. J Natl Cancer Inst 105(9):595–605

    Article  CAS  PubMed  Google Scholar 

  • Lohr JG, Adalsteinsson VA, Cibulskis K, Choudhury AD, Rosenberg M, Cruz-Gordillo P et al (2014) Whole-exome sequencing of circulating tumor cells provides a window into metastatic prostate cancer. Nat Biotech 32(5):479–484

    Article  CAS  Google Scholar 

  • Lu Y, Li SS, Zhu SS, Gong YY, Shi JJ, Xu LL (2017) Methylated DNA/RNA in Body Fluids as Biomarkers for Lung Cancer. Biol Proced Online 19:2

    Google Scholar 

  • Magbanua MJM, Park JW (2014) Advances in genomic characterization of circulating tumor cells. Cancer Metastasis Rev 33(2–3):757–759

    Article  CAS  PubMed  Google Scholar 

  • Maheswaran S, Sequist LV, Nagrath S, Ulkus L, Brannigan B, Collura CV et al (2008) Detection of mutations in EGFR in circulating lung-cancer cells. N Engl J Med 359(4):366–377 PubMed PMID: 18596266

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Man Y, Cao J, Jin S, Xu G, Pan B, Shang L et al (2014) Newly identified biomarkers for detecting circulating tumor cells in lung adenocarcinoma. Tohoku J Exp Med 234(1):29–40

    Article  CAS  PubMed  Google Scholar 

  • Marchetti A, Del Grammastro M, Felicioni L, Malatesta S, Filice G, Centi I et al (2014) Assessment of EGFR mutations in circulating tumor cell preparations from NSCLC patients by next generation sequencing: toward a real-time liquid biopsy for treatment. PLoS ONE 9(8):e103883

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Milaki G, Messaritakis I, Koinis F, Kotsakis A, Apostolaki S, Dermitzaki EK et al (2017) Prognostic value of chemotherapy-resistant CK19mRNA-positive circulating tumor cells in patients with advanced/metastatic non-small cell lung cancer. Cancer Chemother Pharmacol 80(1):101–108

    Article  CAS  PubMed  Google Scholar 

  • Miyamoto DT, Zheng Y, Wittner BS, Lee RJ, Zhu H, Broderick KT et al (2015) RNA-Seq of single prostate CTCs implicates noncanonical Wnt signaling in antiandrogen resistance. Science 349(6254):1351–1356

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Miyamoto DT, Lee RJ, Kalinich M, LiCausi J, Zheng Y, Chen T et al (2018) An RNA-based digital circulating tumor cell signature is predictive of drug response and early dissemination in prostate cancer. Cancer Discov

    Google Scholar 

  • Mohan S, Chemi F, Brady G (2017) Challenges and unanswered questions for the next decade of circulating tumour cell research in lung cancer. Transl Lung Cancer Res 6(4):454–472

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Morrow CJ, Trapani F, Metcalf RL, Bertolini G, Hodgkinson CL, Khandelwal G et al (2016) Tumourigenic non-small-cell lung cancer mesenchymal circulating tumour cells: a clinical case study. Ann Oncol 27(6):1155–1160

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Muinelo-Romay L, Vieito M, Abalo A, Nocelo MA, Baron F, Anido U et al (2014) Evaluation of circulating tumor cells and related events as prognostic factors and surrogate biomarkers in advanced NSCLC patients receiving first-line systemic treatment. Cancers 6(1):153–165

    Article  PubMed  PubMed Central  Google Scholar 

  • Muller V, Stahmann N, Riethdorf S, Rau T, Zabel T, Goetz A et al (2005) Circulating tumor cells in breast cancer: correlation to bone marrow micrometastases, heterogeneous response to systemic therapy and low proliferative activity. Clin Cancer Res 11(10):3678–3685

    Article  PubMed  Google Scholar 

  • Naito T, Tanaka F, Ono A, Yoneda K, Takahashi T, Murakami H et al (2012) Prognostic impact of circulating tumor cells in patients with small cell lung cancer. J Thorac Oncol 7(3):512–519

    Article  PubMed  Google Scholar 

  • Nalejska E, Maczynska E, Lewandowska MA (2014) Prognostic and predictive biomarkers: tools in personalized oncology. Mol Diagn Ther. 18(3):273–284

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Navin NE (2015) The first five years of single-cell cancer genomics and beyond. Genome Res 25

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nel I, Jehn U, Gauler T, Hoffmann A-C (2014) Individual profiling of circulating tumor cell composition in patients with non-small cell lung cancer receiving platinum based treatment. Transl Lung Cancer Res 3(2):100–106

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ni X, Zhuo M, Su Z, Duan J, Gao Y, Wang Z et al (2013) Reproducible copy number variation patterns among single circulating tumor cells of lung cancer patients. Proc Natl Acad Sci 110(52):21083–21088

    Google Scholar 

  • Nicolazzo C, Cristina R, Mancini M, Caponnetto S, Gradilone A, Gandin O et al (2016) Monitoring PD-L1 positive circulating tumor cells in non-small cell lung cancer patients treated with the PD-1 inhibitor Nivolumab. Sci Rep (6):31726

    Google Scholar 

  • Offin M, Chabon JJ, Razavi P, Isbell JM, Rudin CM, Diehn M et al (2017) Capturing genomic evolution of lung cancers through liquid biopsy for circulating tumor DNA. J Oncol. 2017(Figure 1):1–5

    Article  CAS  Google Scholar 

  • O’Flaherty JD, Gray S, Richard D, Fennell D, O’Leary JJ, Blackhall FH et al (2012) Circulating tumour cells, their role in metastasis and their clinical utility in lung cancer. Lung Cancer 76(1):19–25

    Article  PubMed  Google Scholar 

  • O’Hara SM, Smirnov DA, Zweitzig DR, Foulk BW, Doyle GV, Pienta KJ et al (2005) Global gene expression profiling of circulating tumor cells. Proc Am Assoc Cancer Res Annu Meet 46(12):1311

    Google Scholar 

  • Pailler E, Adam J, Barthelemy A, Oulhen M, Auger N, Valent A et al (2013) Detection of circulating tumor cells harboring a unique ALK rearrangement in ALK-positive non-small-cell lung cancer. J Clin Oncol 31(18):2273–2281

    Article  PubMed  Google Scholar 

  • Pailler E, Auger N, Lindsay CR, Vielh P, Islas-Morris-Hernandez A, Borget I et al (2015) High level of chromosomal instability in circulating tumor cells of ROS1-rearranged non-small-cell lung cancer. Ann Oncol 26(7):1408–1415

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pailler E, Oulhen M, Borget I, Remon J, Ross K, Auger N et al (2017) Circulating tumor cells with aberrant ALK copy number predict progression-free survival during crizotinib treatment in ALK-rearranged non-small cell lung cancer patients. Can Res 77(9):2222–2230

    Article  CAS  Google Scholar 

  • Paoletti C, Cani AK, Larios JM, Hovelson DH, Aung K, Darga EP et al (2018) Comprehensive mutation and copy number profiling in archived circulating breast cancer tumor cells documents heterogeneous resistance mechanisms. Cancer Res 78(4):1110–1122. PubMed PMID: 29233927. Pubmed Central PMCID: PMC5815882. Epub 2017/12/14. eng

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Peeters DJ, De Laere B, Van den Eynden GG, Van Laere SJ, Rothe F, Ignatiadis M et al (2013) Semiautomated isolation and molecular characterisation of single or highly purified tumour cells from Cell Search enriched blood samples using dielectrophoretic cell sorting. Br J Cancer 108(6):1358–1367

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Perakis S, Speicher MR (2017) Emerging concepts in liquid biopsies. BMC Med 15(1):017–0840

    Article  CAS  Google Scholar 

  • Pixberg CF, Raba K, Muller F, Behrens B, Honisch E, Niederacher D et al (2017) Analysis of DNA methylation in single circulating tumor cells. Oncogene

    Google Scholar 

  • Punnoose EA, Atwal S, Liu W, Raja R, Fine BM, Hughes BGM et al (2012) Evaluation of circulating tumor cells and circulating tumor DNA in non-small cell lung cancer: association with clinical endpoints in a phase II clinical trial of pertuzumab and erlotinib. Clin Cancer Res 18(8):2391

    Article  CAS  PubMed  Google Scholar 

  • Rhim AD, Mirek ET, Aiello NM, Maitra A, Bailey JM, McAllister F et al (2012) EMT and dissemination precede pancreatic tumor formation. Cell 148(1–2):349–361

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rothwell DG, Smith N, Morris D, Leong HS, Li Y, Carter L et al (2015) Molecular characterisation of SCLC using both circulating tumour DNA and circulating tumour cells isolated from the same whole blood sample. J Thorac Oncol 10(9):S344-S

    Google Scholar 

  • Sato T, Arai E, Kohno T, Takahashi Y, Miyata S, Tsuta K et al (2014) Epigenetic clustering of lung adenocarcinomas based on DNA methylation profiles in adjacent lung tissue: Its correlation with smoking history and chronic obstructive pulmonary disease. Int J Cancer 135(2):319–334

    Article  CAS  PubMed  Google Scholar 

  • Schmidt-hansen M, Berendse S, Hamilton W, Baldwin DR (2017) Lung cancer in symptomatic patients presenting in primary care: a systematic review of risk prediction tools

    Google Scholar 

  • Shaw AT, Yeap BY, Solomon BJ, Riely GJ, Gainor J, Engelman JA et al (2011) Effect of crizotinib on overall survival in patients with advanced non-small-cell lung cancer harbouring ALK gene rearrangement: a retrospective analysis. Lancet Oncol 12(11):1004–1012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Siegmund K, Shibata D (2016) At least two well-spaced samples are needed to genotype a solid tumor. BMC Cancer 16(1):250

    Google Scholar 

  • Sieuwerts AM, Kraan J, Bolt-De Vries J, Van Der Spoel P, Mostert B, Martens JWM et al (2009) Molecular characterization of circulating tumor cells in large quantities of contaminating leukocytes by a multiplex real-time PCR. Breast Cancer Res Treat 118(3):455–468

    Article  CAS  PubMed  Google Scholar 

  • Sinkala E, Sollier-Christen E, Renier C, Rosàs-Canyelles E, Che J, Heirich K et al (2017) Profiling protein expression in circulating tumour cells using microfluidic western blotting. Nat Commun 8:14622

    Google Scholar 

  • Smallwood Sa, Lee HJ, Angermueller C, Krueger F, Saadeh H, Peat J et al (2014) Single-cell genome-wide bisulfite sequencing for assessing epigenetic heterogeneity. Nat Methods 11(8):817–820

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Spits C, Le Caignec C, De Rycke M, Van Haute L, Van Steirteghem A, Liebaers I et al (2006) Whole-genome multiple displacement amplification from single cells. Nat Protocols 1(4):1965–1970

    Article  CAS  PubMed  Google Scholar 

  • Stathopoulou A, Gizi A, Perraki M, Apostolaki S, Malamos N, Mavroudis D et al (2003) Real-time quantification of CK-19 mRNA-positive cells in peripheral blood of breast cancer patients using the lightcycler system real-time quantification of CK-19 mRNA-positive cells in peripheral blood of breast cancer patients using the lightcycler syst. 9:5145–5151

    Google Scholar 

  • Swennenhuis JF, Reumers J, Thys K, Aerssens J (2013) Terstappen LWMM. Efficiency of whole genome amplification of single circulating tumor cells enriched by CellSearch and sorted by FACS. Genome Med 5(11):106. PubMed PMID: PMC3978840

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Thiele JA, Bethel K, Kralickova M, Kuhn P (2017) Circulating tumor cells: fluid surrogates of solid tumors. Annu Rev Pathol 12:419–447

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ting DT, Wittner BS, Ligorio M, Jordan NV, Ajay M, Miyamoto DT et al (2015) Single-cell RNA sequencing identifies extracellular matrix gene expression by pancreatic circulating tumor cells david 8(6):1905–1918

    Google Scholar 

  • Walter K, Holcomb T, Januario T, Du P, Evangelista M, Kartha N et al (2012) DNA methylation profiling defines clinically relevant biological subsets of non-small cell lung cancer. Clin Cancer Res 18(8):2360–2373

    Article  CAS  PubMed  Google Scholar 

  • Wang Z, Wu W, Wang Z, Tang Y, Deng Y, Xu L et al (2016) Ex vivo expansion of circulating lung tumor cells based on one-step microfluidics-based immunomagnetic isolation. Analyst 141(12):3621–3625

    Article  CAS  PubMed  Google Scholar 

  • Wit Sd, Dalum Gv, Lenferink ATM, Tibbe AGJ, Hiltermann TJN, Groen HJM et al (2015) The detection of EpCAM+ and EpCAM–circulating tumor cells. Sci Rep 5:12270

    Google Scholar 

  • Yu M, Bardia A, Aceto N, Bersani F, Madden MW, Donaldson MC et al (2014) Ex vivo culture of circulating breast tumor cells for individualized testing of drug susceptibility. Science 345(6193):216

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang L, Ridgway LD, Wetzel MD, Ngo J, Yin W, Kumar D et al (2013) The Identification and characterization of breast cancer CTCs competent for brain metastasis. Sci Transl Med 5(180):180ra48-ra48

    Article  PubMed  CAS  Google Scholar 

  • Zhang Z, Shiratsuchi H, Lin J, Chen G, Reddy RM, Azizi E et al (2014) Expansion of CTCs from early stage lung cancer patients using a microfluidic co-culture model. Oncotarget 5(23):12383–12397

    PubMed  PubMed Central  Google Scholar 

  • Zhang Y, Tang Y, Sun S, Wang Z, Wu W, Zhao X et al (2015) Single-cell codetection of metabolic activity, intracellular functional proteins, and genetic mutations from rare circulating tumor cells. Anal Chem 87(19):9761–9768

    Article  CAS  PubMed  Google Scholar 

  • Zheng Y, Miyamoto DT, Wittner BS, Sullivan JP, Aceto N, Jordan NV et al (2017) Expression of β-globin by cancer cells promotes cell survival during blood-borne dissemination. Nat Commun 8:14344

    Google Scholar 

  • Zong C, Lu S, Chapman AR, Xie XS (2012) Genome-wide detection of single-nucleotide and copy-number variations of a single human cell. Science 338(6114):1622–1626

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We would like to acknowledge Caroline Dive for her advice in writing this chapter. We would like to also acknowledge the help of the CR-UK Clinical and Experimental Pharmacology Group (C5759/A20971) for their support of this study, as well as the financial support from Medical Research Council Manchester Single Cell Research Centre (MR/M008908/1). FC is funded by Cancer-ID (115749-Cancer-ID), and SM is funded by AstraZeneca (D1330N00013).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ged Brady .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Chemi, F., Mohan, S., Brady, G. (2020). Circulating Tumour Cells in Lung Cancer. In: Schaffner, F., Merlin, JL., von Bubnoff, N. (eds) Tumor Liquid Biopsies. Recent Results in Cancer Research, vol 215. Springer, Cham. https://doi.org/10.1007/978-3-030-26439-0_6

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-26439-0_6

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-26438-3

  • Online ISBN: 978-3-030-26439-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics