Advertisement

Current Oncology Reports

, 20:70 | Cite as

The Present and Future of Liquid Biopsies in Non-Small Cell Lung Cancer: Combining Four Biosources for Diagnosis, Prognosis, Prediction, and Disease Monitoring

  • Jillian Wilhelmina Paulina Bracht
  • Clara Mayo-de-las-Casas
  • Jordi Berenguer
  • Niki KarachaliouEmail author
  • Rafael RosellEmail author
Lung Cancer (H Borghaei, Section Editor)

Abstract

Purpose of Review

Liquid biopsies have potential as tools for diagnosis, prognosis, and prediction of response to therapy. Herein, we will extensively review four liquid biosources, tumor-educated platelets (TEPs), cell-free DNA (cfDNA), circulating tumor cells (CTCs), and extracellular vesicles (EVs) and we will clarify their optimal application in non-small cell lung cancer (NSCLC) diagnosis and therapy.

Recent Findings

Liquid biopsies are a minimally invasive alternative to tissue biopsies—especially important in NSCLC patients—since tumor tissue is often unavailable or insufficient for complete genetic analysis. The main advantages of liquid biopsies include the possibility for repeated sampling, the lower cost, and the fact that they can reflect the complete molecular status of the patient better than a single-site biopsy. This is specifically important for lung adenocarcinoma patients since the detection of specific genetic alterations can predict response to targeted therapies.

Summary

Molecular analysis is currently cardinal for therapy decision-making and disease monitoring in lung cancer patients. Liquid biopsies can make easier our daily clinical practice and if prospectively tested and validated may serve as a means for lung cancer early detection.

Keywords

Liquid biopsy Liquid biosources NSCLC Lung cancer Diagnostic biomarker Prognostic biomarker Predictive biomarker Resistance biomarker TEPs cfDNA ctDNA EVs Exosomes CTCs 

Notes

Funding

The work of Jillian Wilhelmina Paulina Bracht in Pangaea Oncology is supported by a European Grant (ELBA No 765492). Work in Dr. Rosell’s laboratory is partially supported by a grant from La Caixa Foundation, an Instituto de Salud Carlos III grant (RESPONSE, PIE16/00011) and a European Grant (ELBA No 765492).

Compliance with Ethical Standards

Conflict of Interest

Jillian Wilhelmina Paulina Bracht, Clara Mayo-de-las-Casas, Jordi Berenguer, Niki Karachaliou, and Rafael Rosell declare they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin. 2017;67(1):7–30.  https://doi.org/10.3322/caac.21387.PubMedCrossRefPubMedCentralGoogle Scholar
  2. 2.
    Hirsch FR, Scagliotti GV, Mulshine JL, Kwon R, Curran WJ Jr, Wu YL, et al. Lung cancer: current therapies and new targeted treatments. Lancet. 2017;389(10066):299–311.  https://doi.org/10.1016/S0140-6736(16)30958-8.PubMedCrossRefGoogle Scholar
  3. 3.
    Karachaliou N, Sosa AE, Barron FB, Gonzalez Cao M, Santarpia M, Rosell R. Pharmacological management of relapsed/refractory NSCLC with chemical drugs. Expert Opin Pharmacother. 2017;18:1–10.  https://doi.org/10.1080/14656566.2017.1285284.CrossRefGoogle Scholar
  4. 4.
    Rosell R, Karachaliou N. Large-scale screening for somatic mutations in lung cancer. Lancet. 2016;387(10026):1354–6.  https://doi.org/10.1016/S0140-6736(15)01125-3.PubMedCrossRefGoogle Scholar
  5. 5.
    Jordan EJ, Kim HR, Arcila ME, Barron D, Chakravarty D, Gao J, et al. Prospective comprehensive molecular characterization of lung adenocarcinomas for efficient patient matching to approved and emerging therapies. Cancer Discov. 2017;7(6):596–609.  https://doi.org/10.1158/2159-8290.CD-16-1337.PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    • Karachaliou N, Sosa AE, Molina MA, Centelles Ruiz M, Rosell R. Possible application of circulating free tumor DNA in non-small cell lung cancer patients. J Thorac Dis. 2017;9(Suppl 13):S1364–S72.  https://doi.org/10.21037/jtd.2017.09.59. The SLIPP study was used to compare the performance of the Guardant360 NGS panel in detecting genetic alterations in ctDNA versus standard of care tissue testing. Blood and tissue samples from metastatic non-squamous NSCLC patients were collected before first-line chemotherapy and upon progression. PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Senan S, Paul MA, Lagerwaard FJ. Treatment of early-stage lung cancer detected by screening: surgery or stereotactic ablative radiotherapy? Lancet Oncol. 2013;14(7):e270–4.  https://doi.org/10.1016/S1470-2045(12)70592-2.PubMedCrossRefGoogle Scholar
  8. 8.
    Nelson HD, Fu R, Cantor A, Pappas M, Daeges M, Humphrey L. Effectiveness of breast cancer screening: systematic review and meta-analysis to update the 2009 U.S. preventive services task force recommendation. Ann Intern Med. 2016;164(4):244–55.  https://doi.org/10.7326/M15-0969.PubMedCrossRefGoogle Scholar
  9. 9.
    Weller DP, Patnick J, McIntosh HM, Dietrich AJ. Uptake in cancer screening programmes. Lancet Oncol. 2009;10(7):693–9.  https://doi.org/10.1016/S1470-2045(09)70145-7.PubMedCrossRefGoogle Scholar
  10. 10.
    Budenholzer B. Screening for colorectal cancer. Lancet. 1997;349(9048):356–7; author reply 8.  https://doi.org/10.1016/S0140-6736(05)62855-3.PubMedCrossRefGoogle Scholar
  11. 11.
    Schroder FH, Hugosson J, Roobol MJ, Tammela TL, Zappa M, Nelen V, et al. Screening and prostate cancer mortality: results of the European randomised study of screening for prostate cancer (ERSPC) at 13 years of follow-up. Lancet. 2014;384(9959):2027–35.  https://doi.org/10.1016/S0140-6736(14)60525-0.PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Marmot MG, Altman DG, Cameron DA, Dewar JA, Thompson SG, Wilcox M. The benefits and harms of breast cancer screening: an independent review. Br J Cancer. 2013;108(11):2205–40.  https://doi.org/10.1038/bjc.2013.177.PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Karachaliou N, Mayo-de-Las-Casas C, Molina-Vila MA, Rosell R. Real-time liquid biopsies become a reality in cancer treatment. Ann Transl Med. 2015;3(3):36.  https://doi.org/10.3978/j.issn.2305-5839.2015.01.16. PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Siravegna G, Marsoni S, Siena S, Bardelli A. Integrating liquid biopsies into the management of cancer. Nat Rev Clin Oncol. 2017;14(9):531–48.  https://doi.org/10.1038/nrclinonc.2017.14.PubMedCrossRefGoogle Scholar
  15. 15.
    Friedrich MJ. Going with the flow: the promise and challenge of liquid biopsies. JAMA. 2017;318(12):1095–7.  https://doi.org/10.1001/jama.2017.10203.PubMedCrossRefGoogle Scholar
  16. 16.
    Rolfo C, Castiglia M, Hong D, Alessandro R, Mertens I, Baggerman G, et al. Liquid biopsies in lung cancer: the new ambrosia of researchers. Biochim Biophys Acta. 2014;1846(2):539–46.  https://doi.org/10.1016/j.bbcan.2014.10.001.PubMedCrossRefGoogle Scholar
  17. 17.
    •• Cohen JD, Li L, Wang Y, Thoburn C, Afsari B, Danilova L, et al. Detection and localization of surgically resectable cancers with a multi-analyte blood test. Science. 2018;  https://doi.org/10.1126/science.aar3247. This study describes a new multi-analyte blood test based on cfDNA and circulating proteins—called CellSEEK—that may be used to detect and localize surgically resectable cancers.
  18. 18.
    •• Best MG, Sol N, In ’t Veld S, Vancura A, Muller M, Niemeijer AN, et al. Swarm intelligence-enhanced detection of non-small-cell lung cancer using tumor-educated platelets. Cancer Cell. 2017;32(2):238–52 e9.  https://doi.org/10.1016/j.ccell.2017.07.004. In this paper, a Particle-Swarm Optimization algorithm—trained on TEP mRNA from healthy individuals and NSCLC patients—was shown to be able to distinguish between NSCLC patients and healthy controls with an accuracy of 81 and 88% in early- and late-stage NSCLC patients respectively. PubMedCrossRefGoogle Scholar
  19. 19.
    • Best MG, Sol N, Kooi I, Tannous J, Westerman BA, Rustenburg F, et al. RNA-Seq of tumor-educated platelets enables blood-based pan-cancer, multiclass, and molecular pathway cancer diagnostics. Cancer Cell. 2015;28(5):666–76.  https://doi.org/10.1016/j.ccell.2015.09.018. The study demonstrates that TEP mRNA-seq analysis can be used to train a LOOCV SVM algorithm, which can then distinguish between the blood of healthy individuals and cancer patients with an accuracy of 96%. PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Haber DA, Velculescu VE. Blood-based analyses of cancer: circulating tumor cells and circulating tumor DNA. Cancer Discov. 2014;4(6):650–61.  https://doi.org/10.1158/2159-8290.CD-13-1014.PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Bettegowda C, Sausen M, Leary RJ, Kinde I, Wang Y, Agrawal N, et al. Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci Transl Med. 2014;6(224):224ra24.  https://doi.org/10.1126/scitranslmed.3007094.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Diaz LA Jr, Bardelli A. Liquid biopsies: genotyping circulating tumor DNA. J Clin Oncol. 2014;32(6):579–86.  https://doi.org/10.1200/JCO.2012.45.2011.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Leon SA, Shapiro B, Sklaroff DM, Yaros MJ. Free DNA in the serum of cancer patients and the effect of therapy. Cancer Res. 1977;37(3):646–50.PubMedGoogle Scholar
  24. 24.
    Calabuig-Farinas S, Jantus-Lewintre E, Herreros-Pomares A, Camps C. Circulating tumor cells versus circulating tumor DNA in lung cancer—which one will win? Transl Lung Cancer Res. 2016;5(5):466–82.  https://doi.org/10.21037/tlcr.2016.10.02.PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Sanchez-Cespedes M, Monzo M, Rosell R, Pifarre A, Calvo R, Lopez-Cabrerizo MP, et al. Detection of chromosome 3p alterations in serum DNA of non-small-cell lung cancer patients. Ann Oncol. 1998;9(1):113–6.PubMedCrossRefGoogle Scholar
  26. 26.
    Esteller M, Sanchez-Cespedes M, Rosell R, Sidransky D, Baylin SB, Herman JG. Detection of aberrant promoter hypermethylation of tumor suppressor genes in serum DNA from non-small cell lung cancer patients. Cancer Res. 1999;59(1):67–70.PubMedGoogle Scholar
  27. 27.
    Ramirez JL, Sarries C, de Castro PL, Roig B, Queralt C, Escuin D, et al. Methylation patterns and K-ras mutations in tumor and paired serum of resected non-small-cell lung cancer patients. Cancer Lett. 2003;193(2):207–16.PubMedCrossRefGoogle Scholar
  28. 28.
    Ramirez JL, Rosell R, Taron M, Sanchez-Ronco M, Alberola V, de Las Penas R, et al. 14-3-3sigma methylation in pretreatment serum circulating DNA of cisplatin-plus-gemcitabine-treated advanced non-small-cell lung cancer patients predicts survival: the Spanish lung Cancer group. J Clin Oncol. 2005;23(36):9105–12.  https://doi.org/10.1200/JCO.2005.02.2905.PubMedCrossRefGoogle Scholar
  29. 29.
    • Karachaliou N, Mayo-de las Casas C, Queralt C, de Aguirre I, Melloni B, Cardenal F, et al. Association of EGFR L858R mutation in circulating free DNA with survival in the EURTAC trial. JAMA Oncol. 2015;1(2):149–57.  https://doi.org/10.1001/jamaoncol.2014.257. The EGFR L858R mutation was investigated in cfDNA and associated with survival in patients participating in a NSCLC trial comparing efficacy of erlotinib versus chemotherapy. PubMedCrossRefGoogle Scholar
  30. 30.
    Pathak AK, Bhutani M, Kumar S, Mohan A, Guleria R. Circulating cell-free DNA in plasma/serum of lung cancer patients as a potential screening and prognostic tool. Clin Chem. 2006;52(10):1833–42.  https://doi.org/10.1373/clinchem.2005.062893.PubMedCrossRefGoogle Scholar
  31. 31.
    Sacher AG, Paweletz C, Dahlberg SE, Alden RS, O'Connell A, Feeney N, et al. Prospective validation of rapid plasma genotyping for the detection of EGFR and KRAS mutations in advanced lung Cancer. JAMA Oncol. 2016;2(8):1014–22.  https://doi.org/10.1001/jamaoncol.2016.0173.PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Chen T, He R, Hu X, Luo W, Hu Z, Li J, et al. Circulating tumor DNA: a potential biomarker from solid tumors’ monitor to anticancer therapies. Cancer Transl Med. 2017;3(2):64–7.  https://doi.org/10.4103/ctm.ctm_6_17.CrossRefGoogle Scholar
  33. 33.
    Thijssen MA, Swinkels DW, Ruers TJ, de Kok JB. Difference between free circulating plasma and serum DNA in patients with colorectal liver metastases. Anticancer Res. 2002;22(1A):421–5.PubMedGoogle Scholar
  34. 34.
    Jung M, Klotzek S, Lewandowski M, Fleischhacker M, Jung K. Changes in concentration of DNA in serum and plasma during storage of blood samples. Clin Chem. 2003;49(6 Pt 1):1028–9.PubMedCrossRefGoogle Scholar
  35. 35.
    Heitzer E, Auer M, Ulz P, Geigl JB, Speicher MR. Circulating tumor cells and DNA as liquid biopsies. Genome Med. 2013;5(8):73.  https://doi.org/10.1186/gm477. PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Kohn L, Johansson M, Grankvist K, Nilsson J. Liquid biopsies in lung cancer-time to implement research technologies in routine care? Ann Transl Med. 2017;5(13):278.  https://doi.org/10.21037/atm.2017.04.12.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Sorber L, Zwaenepoel K, Deschoolmeester V, Van Schil PE, Van Meerbeeck J, Lardon F, et al. Circulating cell-free nucleic acids and platelets as a liquid biopsy in the provision of personalized therapy for lung cancer patients. Lung Cancer. 2017;107:100–7.  https://doi.org/10.1016/j.lungcan.2016.04.026. PubMedCrossRefGoogle Scholar
  38. 38.
    Vendrell JA, Mau-Them FT, Beganton B, Godreuil S, Coopman P, Solassol J. Circulating cell free tumor DNA detection as a routine tool for lung cancer patient management. Int J Mol Sci. 2017;18(2)  https://doi.org/10.3390/ijms18020264.
  39. 39.
    Perez-Callejo D, Romero A, Provencio M, Torrente M. Liquid biopsy based biomarkers in non-small cell lung cancer for diagnosis and treatment monitoring. Transl Lung Cancer Res. 2016;5(5):455–65.  https://doi.org/10.21037/tlcr.2016.10.07.PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Zhang BO, Xu CW, Shao Y, Wang HT, Wu YF, Song YY, et al. Comparison of droplet digital PCR and conventional quantitative PCR for measuring EGFR gene mutation. Exp Ther Med. 2015;9(4):1383–8.  https://doi.org/10.3892/etm.2015.2221.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Worrillow L, Baskaran P, Care MA, Varghese A, Munir T, Evans PA, et al. An ultra-deep sequencing strategy to detect sub-clonal TP53 mutations in presentation chronic lymphocytic leukaemia cases using multiple polymerases. Oncogene. 2016;35(40):5328–36.  https://doi.org/10.1038/onc.2016.73.PubMedCrossRefGoogle Scholar
  42. 42.
    Cai X, Janku F, Zhan Q, Fan JB. Accessing genetic information with liquid biopsies. Trends Genet. 2015;31(10):564–75.  https://doi.org/10.1016/j.tig.2015.06.001.PubMedCrossRefGoogle Scholar
  43. 43.
    •• Lin E, Rivera-Baez L, Fouladdel S, Yoon HJ, Guthrie S, Wieger J, et al. High-throughput microfluidic labyrinth for the label-free isolation of circulating tumor cells. Cell Syst. 2017;5(3):295–304 e4.  https://doi.org/10.1016/j.cels.2017.08.012. The authors describe a new label-free CTC isolation method, with highest purity among other label-free methods. The blood flows through a labyrinth device with loops and corners to separate different cell types and isolate CTCs. PubMedCrossRefGoogle Scholar
  44. 44.
    Yu Y, Chen Z, Dong J, Wei P, Hu R, Zhou C, et al. Folate receptor-positive circulating tumor cells as a novel diagnostic biomarker in non-small cell lung cancer. Transl Oncol. 2013;6(6):697–702.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Ntouroupi TG, Ashraf SQ, McGregor SB, Turney BW, Seppo A, Kim Y, et al. Detection of circulating tumour cells in peripheral blood with an automated scanning fluorescence microscope. Br J Cancer. 2008;99(5):789–95.  https://doi.org/10.1038/sj.bjc.6604545.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Andreopoulou E, Yang LY, Rangel KM, Reuben JM, Hsu L, Krishnamurthy S, et al. Comparison of assay methods for detection of circulating tumor cells in metastatic breast cancer: AdnaGen AdnaTest BreastCancer Select/Detect versus Veridex CellSearch system. Int J Cancer. 2012;130(7):1590–7.  https://doi.org/10.1002/ijc.26111.PubMedCrossRefGoogle Scholar
  47. 47.
    Hofman V, Long E, Ilie M, Bonnetaud C, Vignaud JM, Flejou JF, et al. Morphological analysis of circulating tumour cells in patients undergoing surgery for non-small cell lung carcinoma using the isolation by size of epithelial tumour cell (ISET) method. Cytopathology. 2012;23(1):30–8.  https://doi.org/10.1111/j.1365-2303.2010.00835.x.PubMedCrossRefGoogle Scholar
  48. 48.
    Punnoose EA, Atwal S, Liu W, Raja R, Fine BM, Hughes BG, et al. 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. 2012;18(8):2391–401.  https://doi.org/10.1158/1078-0432.CCR-11-3148.PubMedCrossRefGoogle Scholar
  49. 49.
    Oxnard GR, Paweletz CP, Kuang Y, Mach SL, O'Connell A, Messineo MM, et al. Noninvasive detection of response and resistance in EGFR-mutant lung cancer using quantitative next-generation genotyping of cell-free plasma DNA. Clin Cancer Res. 2014;20(6):1698–705.  https://doi.org/10.1158/1078-0432.CCR-13-2482.PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    •• Mayo-de-las-Casas C, Jordana-Ariza N, Garzon-Ibanez M, Balada-Bel A, Bertran-Alamillo J, Viteri-Ramirez S, et al. Large scale, prospective screening of EGFR mutations in the blood of advanced NSCLC patients to guide treatment decisions. Ann Oncol. 2017;0:1–8.  https://doi.org/10.1093/annonc/mdx288. Often tumor tissue if unavailable or insufficient for genetic analysis. Therefore, this study investigated the use of cfDNA as a surrogate for tumor tissue to select patients for the treatment with EGFR-TKIs. CrossRefGoogle Scholar
  51. 51.
    • Malapelle U, Mayo de-Las-Casas C, Rocco D, Garzon M, Pisapia P, Jordana-Ariza N, et al. Development of a gene panel for next-generation sequencing of clinically relevant mutations in cell-free DNA from cancer patients. Br J Cancer. 2017;116(6):802–10.  https://doi.org/10.1038/bjc.2017.8. A gene panel (“SiRe”) based on ultra-deep sequencing of ctDNA was created to detect 568 mutations in six different genes involved in NSCLC, with sensitivity and analytical specificity of 90.5 and 100%, respectively. PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Douillard JY, Ostoros G, Cobo M, Ciuleanu T, Cole R, McWalter G, et al. Gefitinib treatment in EGFR mutated caucasian NSCLC: circulating-free tumor DNA as a surrogate for determination of EGFR status. J Thorac Oncol. 2014;9(9):1345–53.  https://doi.org/10.1097/JTO.0000000000000263.PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    Wu YL, Zhou C, Liam CK, Wu G, Liu X, Zhong Z, et al. 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. Ann Oncol. 2015;26(9):1883–9.  https://doi.org/10.1093/annonc/mdv270.PubMedCrossRefGoogle Scholar
  54. 54.
    Park K, Yu CJ, Kim SW, Lin MC, Sriuranpong V, Tsai CM, et al. First-line erlotinib therapy until and beyond response evaluation criteria in solid tumors progression in Asian patients with epidermal growth factor receptor mutation-positive non-small-cell lung Cancer: the ASPIRATION study. JAMA Oncol. 2016;2(3):305–12.  https://doi.org/10.1001/jamaoncol.2015.4921.PubMedCrossRefGoogle Scholar
  55. 55.
    Goss G, Tsai CM, Shepherd FA, Bazhenova L, Lee JS, Chang GC, et al. Osimertinib for pretreated EGFR Thr790Met-positive advanced non-small-cell lung cancer (AURA2): a multicentre, open-label, single-arm, phase 2 study. Lancet Oncol. 2016;17(12):1643–52.  https://doi.org/10.1016/S1470-2045(16)30508-3.PubMedCrossRefGoogle Scholar
  56. 56.
    Mok T, Ladrera G, Srimuninnimit V, Sriuranpong V, Yu CJ, Thongprasert S, et al. Tumor marker analyses from the phase III, placebo-controlled, FASTACT-2 study of intercalated erlotinib with gemcitabine/platinum in the first-line treatment of advanced non-small-cell lung cancer. Lung Cancer. 2016;98:1–8.  https://doi.org/10.1016/j.lungcan.2016.04.023. PubMedCrossRefGoogle Scholar
  57. 57.
    Lanman RB, Mortimer SA, Zill OA, Sebisanovic D, Lopez R, Blau S, et al. Analytical and clinical validation of a digital sequencing panel for quantitative, highly accurate evaluation of cell-free circulating tumor DNA. PLoS One. 2015;10(10):e0140712.  https://doi.org/10.1371/journal.pone.0140712.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Cristofanilli M, Budd GT, Ellis MJ, Stopeck A, Matera J, Miller MC, et al. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med. 2004;351(8):781–91.  https://doi.org/10.1056/NEJMoa040766.PubMedCrossRefGoogle Scholar
  59. 59.
    Krebs MG, Hou JM, Sloane R, Lancashire L, Priest L, Nonaka D, et al. Analysis of circulating tumor cells in patients with non-small cell lung cancer using epithelial marker-dependent and -independent approaches. J Thorac Oncol. 2012;7(2):306–15.  https://doi.org/10.1097/JTO.0b013e31823c5c16.PubMedCrossRefGoogle Scholar
  60. 60.
    Alix-Panabieres C, Pantel K. Characterization of single circulating tumor cells. FEBS Lett. 2017;591(15):2241–50.  https://doi.org/10.1002/1873-3468.12662.PubMedCrossRefGoogle Scholar
  61. 61.
    Larrea E, Sole C, Manterola L, Goicoechea I, Armesto M, Arestin M, et al. New concepts in cancer biomarkers: circulating miRNAs in liquid biopsies. Int J Mol Sci. 2016;17(5)  https://doi.org/10.3390/ijms17050627.
  62. 62.
    Maheswaran S, Haber DA. Circulating tumor cells: a window into cancer biology and metastasis. Curr Opin Genet Dev. 2010;20(1):96–9.  https://doi.org/10.1016/j.gde.2009.12.002.PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Negin BP, Cohen SJ. Circulating tumor cells in colorectal cancer: past, present, and future challenges. Curr Treat Options in Oncol. 2010;11(1–2):1–13.  https://doi.org/10.1007/s11864-010-0115-3.CrossRefGoogle Scholar
  64. 64.
    Galletti G, Portella L, Tagawa ST, Kirby BJ, Giannakakou P, Nanus DM. Circulating tumor cells in prostate cancer diagnosis and monitoring: an appraisal of clinical potential. Mol Diagn Ther. 2014;18(4):389–402.  https://doi.org/10.1007/s40291-014-0101-8.PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Maheswaran S, Sequist LV, Nagrath S, Ulkus L, Brannigan B, Collura CV, et al. Detection of mutations in EGFR in circulating lung-cancer cells. N Engl J Med. 2008;359(4):366–77.  https://doi.org/10.1056/NEJMoa0800668.PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Krebs MG, Sloane R, Priest L, Lancashire L, Hou JM, Greystoke A, et al. Evaluation and prognostic significance of circulating tumor cells in patients with non-small-cell lung cancer. J Clin Oncol. 2011;29(12):1556–63.  https://doi.org/10.1200/JCO.2010.28.7045.PubMedCrossRefGoogle Scholar
  67. 67.
    Juan O, Vidal J, Gisbert R, Munoz J, Macia S, Gomez-Codina J. Prognostic significance of circulating tumor cells in advanced non-small cell lung cancer patients treated with docetaxel and gemcitabine. Clin Transl Oncol. 2014;16(7):637–43.  https://doi.org/10.1007/s12094-013-1128-8.PubMedCrossRefGoogle Scholar
  68. 68.
    Dorsey JF, Kao GD, MacArthur KM, Ju M, Steinmetz D, Wileyto EP, et al. Tracking viable circulating tumor cells (CTCs) in the peripheral blood of non-small cell lung cancer (NSCLC) patients undergoing definitive radiation therapy: pilot study results. Cancer. 2015;121(1):139–49.  https://doi.org/10.1002/cncr.28975. PubMedCrossRefGoogle Scholar
  69. 69.
    Rolle A, Gunzel R, Pachmann U, Willen B, Hoffken K, Pachmann K. Increase in number of circulating disseminated epithelial cells after surgery for non-small cell lung cancer monitored by MAINTRAC(R) is a predictor for relapse: a preliminary report. World J Surg Oncol. 2005;3(1):18.  https://doi.org/10.1186/1477-7819-3-18. PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    George JN. Platelets. Lancet. 2000;355(9214):1531–9.  https://doi.org/10.1016/S0140-6736(00)02175-9.PubMedCrossRefPubMedCentralGoogle Scholar
  71. 71.
    Nash GF, Turner LF, Scully MF, Kakkar AK. Platelets and cancer. Lancet Oncol. 2002;3(7):425–30.PubMedCrossRefGoogle Scholar
  72. 72.
    Menter DG, Tucker SC, Kopetz S, Sood AK, Crissman JD, Honn KV. Platelets and cancer: a casual or causal relationship: revisited. Cancer Metastasis Rev. 2014;33(1):231–69.  https://doi.org/10.1007/s10555-014-9498-0.PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    McAllister SS, Weinberg RA. The tumour-induced systemic environment as a critical regulator of cancer progression and metastasis. Nat Cell Biol. 2014;16(8):717–27.  https://doi.org/10.1038/ncb3015.PubMedCrossRefGoogle Scholar
  74. 74.
    Nilsson RJ, Balaj L, Hulleman E, van Rijn S, Pegtel DM, Walraven M, et al. Blood platelets contain tumor-derived RNA biomarkers. Blood. 2011;118(13):3680–3.  https://doi.org/10.1182/blood-2011-03-344408.PubMedCrossRefGoogle Scholar
  75. 75.
    • Nilsson RJ, Karachaliou N, Berenguer J, Gimenez-Capitan A, Schellen P, Teixido C, et al. Rearranged EML4-ALK fusion transcripts sequester in circulating blood platelets and enable blood-based crizotinib response monitoring in non-small-cell lung cancer. Oncotarget. 2016;7(1):1066–75.  https://doi.org/10.18632/oncotarget.6279. The EML4-ALK rearrangement can be found in blood platelets of NSCLC patients. Moreover, it was possible to predict therapy resistance based on blood platelet analysis, 2 months before this could be seen radiographically. PubMedCrossRefGoogle Scholar
  76. 76.
    Leslie M. Cell biology. Beyond clotting: the powers of platelets. Science. 2010;328(5978):562–4.  https://doi.org/10.1126/science.328.5978.562. PubMedCrossRefGoogle Scholar
  77. 77.
    Hoffman M, Monroe DM, Roberts HR. A rapid method to isolate platelets from human blood by density gradient centrifugation. Am J Clin Pathol. 1992;98(5):531–3.PubMedCrossRefGoogle Scholar
  78. 78.
    Mustard JF, Kinlough-Rathbone RL, Packham MA. Isolation of human platelets from plasma by centrifugation and washing. Methods Enzymol. 1989;169:3–11.PubMedCrossRefGoogle Scholar
  79. 79.
    Skog J, Wurdinger T, van Rijn S, Meijer DH, Gainche L, Sena-Esteves M, et al. Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol. 2008;10(12):1470–6.  https://doi.org/10.1038/ncb1800.PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Reclusa P, Taverna S, Pucci M, Durendez E, Calabuig S, Manca P, et al. Exosomes as diagnostic and predictive biomarkers in lung cancer. J Thorac Dis. 2017;9(Suppl 13):S1373–S82.  https://doi.org/10.21037/jtd.2017.10.67. PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    •• Nabet BY, Qiu Y, Shabason JE, Wu TJ, Yoon T, Kim BC, et al. Exosome RNA unshielding couples stromal activation to pattern recognition receptor signaling in Cancer. Cell. 2017;170(2):352–66 e13.  https://doi.org/10.1016/j.cell.2017.06.031. The study describes the analysis of specific exosome-derived RNAs, which were shown to promote tumor growth and induce therapy resistance in breast cancer patients. Moreover, the RNA isolated from exosomes may be used as a diagnostic biomarker for cancer. PubMedCrossRefGoogle Scholar
  82. 82.
    Raposo G, Stoorvogel W. Extracellular vesicles: exosomes, microvesicles, and friends. J Cell Biol. 2013;200(4):373–83.  https://doi.org/10.1083/jcb.201211138.PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Munson P, Shukla A. Exosomes: potential in cancer diagnosis and therapy. Medicines (Basel). 2015;2(4):310–27.  https://doi.org/10.3390/medicines2040310.CrossRefGoogle Scholar
  84. 84.
    Jin X, Chen Y, Chen H, Fei S, Chen D, Cai X, et al. Evaluation of tumor-derived exosomal miRNA as potential diagnostic biomarkers for early-stage non-small cell lung cancer using next-generation sequencing. Clin Cancer Res. 2017;23(17):5311–9.  https://doi.org/10.1158/1078-0432.CCR-17-0577.PubMedCrossRefGoogle Scholar
  85. 85.
    Jakobsen KR, Paulsen BS, Baek R, Varming K, Sorensen BS, Jorgensen MM. Exosomal proteins as potential diagnostic markers in advanced non-small cell lung carcinoma. J Extracell Vesicles. 2015;4:26659.  https://doi.org/10.3402/jev.v4.26659.PubMedCrossRefGoogle Scholar
  86. 86.
    Thakur BK, Zhang H, Becker A, Matei I, Huang Y, Costa-Silva B, et al. Double-stranded DNA in exosomes: a novel biomarker in cancer detection. Cell Res. 2014;24(6):766–9.  https://doi.org/10.1038/cr.2014.44.PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    National Lung Screening Trial Research T, Aberle DR, Adams AM, Berg CD, Black WC, Clapp JD, et al. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med. 2011;365(5):395–409.  https://doi.org/10.1056/NEJMoa1102873. CrossRefGoogle Scholar
  88. 88.
    Saghir Z, Dirksen A, Ashraf H, Bach KS, Brodersen J, Clementsen PF, et al. CT screening for lung cancer brings forward early disease. The randomised Danish Lung Cancer Screening Trial: status after five annual screening rounds with low-dose CT. Thorax. 2012;67(4):296–301.  https://doi.org/10.1136/thoraxjnl-2011-200736.PubMedCrossRefGoogle Scholar
  89. 89.
    Infante M, Cavuto S, Lutman FR, Passera E, Chiarenza M, Chiesa G, et al. Long-term follow-up results of the DANTE trial, a randomized study of lung cancer screening with spiral computed tomography. Am J Respir Crit Care Med. 2015;191(10):1166–75.  https://doi.org/10.1164/rccm.201408-1475OC.PubMedCrossRefGoogle Scholar
  90. 90.
    Pastorino U, Rossi M, Rosato V, Marchiano A, Sverzellati N, Morosi C, et al. Annual or biennial CT screening versus observation in heavy smokers: 5-year results of the MILD trial. Eur J Cancer Prev. 2012;21(3):308–15.  https://doi.org/10.1097/CEJ.0b013e328351e1b6.PubMedCrossRefGoogle Scholar
  91. 91.
    van Klaveren RJ, Oudkerk M, Prokop M, Scholten ET, Nackaerts K, Vernhout R, et al. Management of lung nodules detected by volume CT scanning. N Engl J Med. 2009;361(23):2221–9.  https://doi.org/10.1056/NEJMoa0906085.PubMedCrossRefGoogle Scholar
  92. 92.
    Ru Zhao Y, Xie X, de Koning HJ, Mali WP, Vliegenthart R, Oudkerk M. NELSON lung cancer screening study. Cancer Imaging 2011;11 Spec No A:S79–84.  https://doi.org/10.1102/1470-7330.2011.9020.
  93. 93.
    Pedersen JH, Ashraf H. Implementation and organization of lung cancer screening. Ann Transl Med. 2016;4(8):152.  https://doi.org/10.21037/atm.2016.03.59.PubMedPubMedCentralCrossRefGoogle Scholar
  94. 94.
    Wu GX, Raz DJ, Brown L, Sun V. Psychological burden associated with lung cancer screening: a systematic review. Clin Lung Cancer. 2016;17(5):315–24.  https://doi.org/10.1016/j.cllc.2016.03.007.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Jillian Wilhelmina Paulina Bracht
    • 1
  • Clara Mayo-de-las-Casas
    • 1
  • Jordi Berenguer
    • 1
  • Niki Karachaliou
    • 1
    • 2
    Email author
  • Rafael Rosell
    • 1
    • 3
    • 4
    • 5
    Email author
  1. 1.Pangaea Oncology, Laboratory of Molecular BiologyQuirón-Dexeus University InstituteBarcelonaSpain
  2. 2.Instituto Oncológico Dr Rosell (IOR)University Hospital Sagrat Cor, QuironSalud GroupBarcelonaSpain
  3. 3.Institut Català d’OncologiaHospital Germans Trias i PujolBadalonaSpain
  4. 4.Institut d’Investigació en Ciències Germans Trias i PujolBadalonaSpain
  5. 5.Instituto Oncológico Dr Rosell (IOR)Quirón-Dexeus University InstituteBarcelonaSpain

Personalised recommendations