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Molecular Diagnosis & Therapy
Published in: Molecular Diagnosis & Therapy 5/2016

01-10-2016 | Review Article

Liquid Biopsies in Oncology and the Current Regulatory Landscape

Authors: Lindsay N. Strotman, Lori M. Millner, Roland Valdes Jr., Mark W. Linder

Published in: Molecular Diagnosis & Therapy | Issue 5/2016

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Abstract

There is a profound need in oncology to detect cancer earlier, guide individualized therapies, and better monitor progress during treatment. Currently, some of this information can be achieved through solid tissue biopsy and imaging. However, these techniques are limited because of the invasiveness of the procedure and the size of the tumor. A liquid biopsy can overcome these barriers as its non-invasive nature allows samples to be collected over time. Liquid biopsies may also allow earlier detection than traditional imaging. Liquid biopsies include the analysis of circulating tumor cells (CTCs), cell-free nucleic acid (cfNA), or extracellular vesicles obtained from a variety of biofluids, such as peripheral blood. In this review, we discuss different liquid biopsy types and how they fit into the current regulatory landscape.
Literature
1.
Crowley E, Di Nicolantonio F, Loupakis F, Bardelli A. Liquid biopsy: monitoring cancer-genetics in the blood. Nat Rev Clin Oncol. 2013;10(8):472–84.CrossRefPubMed
2.
3.
Gerlinger M, Rowan AJ, Horswell S, Larkin J, et al. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med. 2012;366(10):883–92.CrossRefPubMedPubMedCentral
4.
Ashworth TR. A case of cancer in which cells similar to those in the tumours were seen in the blood after death. Aust Med J. 1896;14:146–7.
5.
Mandel P, Metais P. C R Seances Soc Biol Fil. 1948;142(3–4):241–3.PubMed
6.
Raj DA, et al. A multiplex quantitative proteomics strategy for protein biomarker studies in urinary exosomes. Kidney Int. 2012;81(12):1263–72.CrossRefPubMed
7.
Wiggins RC, et al. Procoagulant activity in normal human urine associated with subcellular particles. Kidney Int. 1986;29(2):591–7.CrossRefPubMed
8.
Asea A, et al. Heat shock protein-containing exosomes in mid-trimester amniotic fluids. J Reprod Immunol. 2008;79(1):12–7.CrossRefPubMed
9.
Witwer KW, Buzás EI, Bemis LT, et al. Standardization of sample collection, isolation and analysis methods in extracellular vesicle research. J Extracell Vesicles. 2013;2. doi:10.​3402/​jev.​v2i0.​20360.
10.
Caby MP, et al. Exosomal-like vesicles are present in human blood plasma. Int Immunol. 2005;17(7):879–87.CrossRefPubMed
11.
12.
Douillard JY, et al. First-line gefitinib in Caucasian EGFR mutation-positive NSCLC patients: a phase-IV, open-label, single-arm study. Br J Cancer. 2014;110(1):55–62.CrossRefPubMed
13.
Cristofanilli M, et al. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med. 2004;351(8):781–91.CrossRefPubMed
14.
Fidler IJ. The pathogenesis of cancer metastasis: the ‘seed and soil’ hypothesis revisited. Nat Rev Cancer. 2003;3(6):453–8.CrossRefPubMed
15.
Dunn GP, Old LJ, Schreiber RD. The immunobiology of cancer immunosurveillance and immunoediting. Immunity. 2004;21(2):137–48.CrossRefPubMed
16.
17.
Hayes DF, et al. Circulating tumor cells at each follow-up time point during therapy of metastatic breast cancer patients predict progression-free and overall survival. Clin Cancer Res. 2006;12(14 Pt 1):4218–24.CrossRefPubMed
18.
Danila DC, et al. Circulating tumor cell number and prognosis in progressive castration-resistant prostate cancer. Clin Cancer Res. 2007;13(23):7053–8.CrossRefPubMed
19.
Cohen SJ, et al. Relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer. J Clin Oncol. 2008;26(19):3213–21.CrossRefPubMed
20.
Millner LM, Linder MW, Valdes R Jr. Circulating tumor cells: a review of present methods and the need to identify heterogeneous phenotypes. Ann Clin Lab Sci. 2013;43(3):295–304.PubMed
21.
22.
Vona G, et al. Isolation by size of epithelial tumor cells: a new method for the immunomorphological and molecular characterization of circulating tumor cells. Am J Pathol. 2000;156(1):57–63.CrossRefPubMedPubMedCentral
23.
Ferreira MM, Ramani VC, Jeffrey SS. Circulating tumor cell technologies. Mol Oncol. 2016;10(3):374–94.CrossRefPubMed
24.
Fizazi K, et al. High detection rate of circulating tumor cells in blood of patients with prostate cancer using telomerase activity. Ann Oncol. 2007;18(3):518–21.CrossRefPubMed
25.
Stahlberg A, Bengtsson M. Single-cell gene expression profiling using reverse transcription quantitative real-time PCR. Methods. 2010;50(4):282–8.CrossRefPubMed
26.
Hodgkinson CL, et al. Tumorigenicity and genetic profiling of circulating tumor cells in small-cell lung cancer. Nat Med. 2014;20(8):897–903.CrossRefPubMed
27.
28.
Riethdorf S, et al. Detection of circulating tumor cells in peripheral blood of patients with metastatic breast cancer: a validation study of the Cell Search system. Clin Cancer Res. 2007;13(3):920–8.CrossRefPubMed
29.
30.
31.
Maimonis P, et al. Poster no. 4898. American Association of Cancer Research 102nd Annual Meeting, Orlando, Florida, April 2–6 2011.
32.
Gabriel MT, et al. Circulating tumor cells: a review of non-EpCAM-based approaches for cell enrichment and isolation. Clin Chem. 2016;62(4):571–81.CrossRefPubMed
33.
Vasioukhin V, et al. Point mutations of the N-ras gene in the blood plasma DNA of patients with myelodysplastic syndrome or acute myelogenous leukaemia. Br J Haematol. 1994;86(4):774–9.CrossRefPubMed
34.
Sorenson GD, et al. Soluble normal and mutated DNA sequences from single-copy genes in human blood. Cancer Epidemiol Biomark Prev. 1994;3(1):67–71.
35.
Fleischhacker M, Schmidt B. Circulating nucleic acids (CNAs) and cancer: a survey. Biochim Biophys Acta. 2007;1775(1):181–232.PubMed
36.
Medicine Kaiser J. Keeping tabs on tumor DNA. Science. 2010;327(5969):1074.CrossRef
37.
38.
Castells A, et al. K-ras mutations in DNA extracted from the plasma of patients with pancreatic carcinoma: diagnostic utility and prognostic significance. J Clin Oncol. 1999;17(2):578–84.PubMed
39.
Shinozaki M, et al. Utility of circulating B-RAF DNA mutation in serum for monitoring melanoma patients receiving biochemotherapy. Clin Cancer Res. 2007;13(7):2068–74.CrossRefPubMedPubMedCentral
40.
Bettegowda C, et al. Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci Transl Med. 2014;6(224):224ra24.
41.
Esposito A, et al. Monitoring tumor-derived cell-free DNA in patients with solid tumors: clinical perspectives and research opportunities. Cancer Treat Rev. 2014;40(5):648–55.CrossRefPubMed
42.
Gahan PB, Swaminathan R. Circulating nucleic acids in plasma and serum. Recent developments. Ann N Y Acad Sci. 2008;1137:1–6.CrossRefPubMed
43.
Schwarzenbach H, Hoon DS, Pantel K. Cell-free nucleic acids as biomarkers in cancer patients. Nat Rev Cancer. 2011;11(6):426–37.CrossRefPubMed
44.
Anker P, et al. Circulating nucleic acids in plasma or serum. Clin Chim Acta. 2001;313(1–2):143–6.CrossRefPubMed
45.
Allen D, et al. Role of cell-free plasma DNA as a diagnostic marker for prostate cancer. Ann N Y Acad Sci. 2004;1022:76–80.CrossRefPubMed
46.
Chun FK, et al. Circulating tumour-associated plasma DNA represents an independent and informative predictor of prostate cancer. BJU Int. 2006;98(3):544–8.CrossRefPubMed
47.
Sunami E, et al. Quantification of LINE1 in circulating DNA as a molecular biomarker of breast cancer. Ann N Y Acad Sci. 2008;1137:171–4.CrossRefPubMed
48.
Schwarzenbach H, et al. Detection and monitoring of cell-free DNA in blood of patients with colorectal cancer. Ann N Y Acad Sci. 2008;1137:190–6.CrossRefPubMed
49.
50.
Umetani N, et al. Prediction of breast tumor progression by integrity of free circulating DNA in serum. J Clin Oncol. 2006;24(26):4270–6.CrossRefPubMed
51.
Fleischhacker M, et al. Methods for isolation of cell-free plasma DNA strongly affect DNA yield. Clin Chim Acta. 2011;412(23–24):2085–8.CrossRefPubMed
52.
Slatko BE, Hiraizumi Y. Mutation induction in the male recombination strains of Drosophila melanogaster. Genetics. 1973;75(4):643–9.PubMedPubMedCentral
53.
Sonnenberg A, et al. Dielectrophoretic isolation and detection of cancer-related circulating cell-free DNA biomarkers from blood and plasma. Electrophoresis. 2014;35(12–13):1828–36.CrossRefPubMedPubMedCentral
54.
Lam DC, et al. Plasma EGFR mutation detection associated with survival outcomes in advanced-stage lung cancer. Clin Lung Cancer. 2015;16(6):507–13.CrossRefPubMed
55.
56.
Santiago-Dieppa DR, et al. Extracellular vesicles as a platform for ‘liquid biopsy’ in glioblastoma patients. Expert Rev Mol Diagn. 2014;14(7):819–25.CrossRefPubMedPubMedCentral
57.
Yanez-Mo M, et al. Biological properties of extracellular vesicles and their physiological functions. J Extracell Vesicles. 2015;4:27066.PubMed
58.
Andaloussi SEL, Mäger I, Breakefield XO, Wood MJ. Extracellular vesicles: biology and emerging therapeutic opportunities. Nat Rev Drug Discov. 2013;12(5):347–57.CrossRef
59.
van der Pol E, et al. Classification, functions, and clinical relevance of extracellular vesicles. Pharmacol Rev. 2012;64(3):676–705.CrossRefPubMed
60.
Akers JC, et al. Biogenesis of extracellular vesicles (EV): exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies. J Neurooncol. 2013;113(1):1–11.CrossRefPubMed
61.
Minciacchi VR, Freeman MR, Di Vizio D. Extracellular vesicles in cancer: exosomes, microvesicles and the emerging role of large oncosomes. Semin Cell Dev Biol. 2015;40:41–51.CrossRefPubMedPubMedCentral
62.
Enderle D, et al. Characterization of RNA from exosomes and other extracellular vesicles isolated by a novel spin column-based method. PLoS One. 2015;10(8):e0136133.CrossRefPubMedPubMedCentral
63.
Tauro BJ, et al. Comparison of ultracentrifugation, density gradient separation, and immunoaffinity capture methods for isolating human colon cancer cell line LIM1863-derived exosomes. Methods. 2012;56(2):293–304.CrossRefPubMed
64.
65.
van der Pol E, et al. Optical and non-optical methods for detection and characterization of microparticles and exosomes. J Thromb Haemost. 2010;8(12):2596–607.CrossRefPubMed
66.
Dragovic RA, et al. Sizing and phenotyping of cellular vesicles using nanoparticle tracking analysis. Nanomedicine. 2011;7(6):780–8.PubMedPubMedCentral
67.
Filipe V, Hawe A, Jiskoot W. Critical evaluation of nanoparticle tracking analysis (NTA) by NanoSight for the measurement of nanoparticles and protein aggregates. Pharm Res. 2010;27(5):796–810.CrossRefPubMedPubMedCentral
68.
69.
Garza-Licudine E, et al. Portable nanoparticle quantization using a resizable nanopore instrument—the IZON qNano. Conf Proc IEEE Eng Med Biol Soc. 2010;2010:5736–9.PubMed
70.
de Vrij J, et al. Quantification of nanosized extracellular membrane vesicles with scanning ion occlusion sensing. Nanomedicine (Lond). 2013;8(9):1443–58.CrossRef
71.
van der Vlist EJ, et al. Fluorescent labeling of nano-sized vesicles released by cells and subsequent quantitative and qualitative analysis by high-resolution flow cytometry. Nat Protoc. 2012;7(7):1311–26.CrossRefPubMed
72.
73.
Framework for Regulatory Oversight of Laboratory Developed Tests (LDTs) DRAFT GUIDANCE, F.a.D. Adminstration, Editor. 2014.
74.
Clinical Laboratory Improvement Amendments of 1988. 1988, US Government Publishing Office.
75.
76.
77.
78.
HR 11124 An Act to amend the Federal Food, Drug, and Cosmetic Act to provide for the safety and effectiveness of medical devices intended for human use, and for other purposes. Library of Congress Thomas; 1976.
79.
80.
Metadata
Title
Liquid Biopsies in Oncology and the Current Regulatory Landscape
Authors
Lindsay N. Strotman
Lori M. Millner
Roland Valdes Jr.
Mark W. Linder
Publication date
01-10-2016
Publisher
Springer International Publishing
Published in
Molecular Diagnosis & Therapy / Issue 5/2016
Print ISSN: 1177-1062
Electronic ISSN: 1179-2000
DOI
https://doi.org/10.1007/s40291-016-0220-5

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