Liquid biopsy

A liquid biopsy, also known as fluid biopsy or fluid phase biopsy, is the sampling and analysis of non-solid biological tissue, primarily blood.[1] Like traditional biopsy this type of technique is mainly used as a diagnostic and monitoring tool for diseases such as cancer, with the added benefit of being largely non-invasive. Therefore, it can also be done more frequently which can better track tumors and mutations over a duration of time. It may also be used to validate the efficiency of a cancer treatment drug by taking multiple liquid biopsy samples in the span of a few weeks. The technology may also prove beneficial for patients after treatment to monitor relapse.[2]

Liquid biopsy
SynonymsFluid biopsy
Purposeanalysis of non-solid biological tissue

Although only CellSearch method for enumeration of circulating tumor cells in metastatic breast, metastatic colon, and metastatic prostate cancer has been validated and approved by the FDA as a useful prognostic method,[3] its clinical implementation is not yet widespread.[4]

Types

There are several types of liquid biopsy methods; method selection depends on the condition that is being studied.

A wide variety of biomarkers may be studied to detect or monitor other diseases. For example, isolation of protoporphyrin IX from blood samples can be used as a diagnostic tool for atherosclerosis.[7] When studying the central nervous system, cerebrospinal fluid may be sampled instead of blood.[8][9]

How it works
Main articles: Circulating tumor cell § Detection methods, and Circulating tumor DNA § Analysis of ctDNA

When tumor cells die, they release ctDNA into the blood.[10] Cancer mutations in ctDNA mirror those found in traditional tumor biopsies, which allows them to be used as molecular biomarkers to track the disease.[11] Scientists can purify and then analyze ctDNA using next-generation sequencing (NGS) or PCR-based methods such as digital PCR.[12] NGS-based methods provide a comprehensive view of a cancer’s genetic makeup and is especially useful in diagnosis while digital PCR offers a more targeted approach especially well-suited for detecting minimal residual disease and for monitoring treatment response and disease progression.[13][14] Recent progress in epigenetics has expanded the use of liquid biopsy for the detection of early-stage cancers, including by approaches such as Cancer Likelihood in Plasma (CLiP) .[15]

Liquid biopsies can detect changes in tumor burden months or years before conventional imaging tests can, making them suitable for early tumor detection, monitoring, and detection of resistance mutations.[16][17][18]

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See also

References
  1. Crowley, Emily; Di Nicolantonio, Federica; Loupakis, Fotios; Bardelli, Alberto (9 July 2013). "Liquid biopsy: monitoring cancer-genetics in the blood". Nature Reviews Clinical Oncology. 10 (8): 472–484. doi:10.1038/nrclinonc.2013.110. PMID 23836314.
  2. "Understanding cancer's unruly origins helps early diagnosis". The Economist. Retrieved 2017-09-29.
  3. Karachaliou, N; Mayo-de-Las-Casas, C; Molina-Vila, MA; Rosell, R (March 2015). "Real-time liquid biopsies become a reality in cancer treatment". Annals of Translational Medicine. 3 (3): 36. doi:10.3978/j.issn.2305-5839.2015.01.16. PMC 4356857. PMID 25815297.
  4. Gingras, Isabelle; Salgado, Roberto; Ignatiadis, Michail (November 2015). "Liquid biopsy: will it be the 'magic tool' for monitoring response of solid tumors to anticancer therapies?". Current Opinion in Oncology. 27 (6): 560–567. doi:10.1097/CCO.0000000000000223. PMID 26335664.
  5. Heitzer, E.; Ulz, P.; Geigl, J. B. (11 November 2014). "Circulating Tumor DNA as a Liquid Biopsy for Cancer". Clinical Chemistry. 61 (1): 112–123. doi:10.1373/clinchem.2014.222679. PMID 25388429.
  6. Wan, Jonathan C. M.; Massie, Charles; Garcia-Corbacho, Javier; Mouliere, Florent; Brenton, James D.; Caldas, Carlos; Pacey, Simon; Baird, Richard; Rosenfeld, Nitzan (24 February 2017). "Liquid biopsies come of age: towards implementation of circulating tumour DNA". Nature Reviews Cancer. 17 (4): 223–238. doi:10.1038/nrc.2017.7. PMID 28233803.
  7. Nascimento da Silva, Monica; Sicchieri, Letícia Bonfante; Rodrigues de Oliveira Silva, Flávia; Andrade, Maira Franco; Courrol, Lilia Coronato (2014). "Liquid biopsy of atherosclerosis using protoporphyrin IX as a biomarker". The Analyst. 139 (6): 1383–8. Bibcode:2014Ana...139.1383N. doi:10.1039/c3an01945d. PMID 24432352.
  8. Pyykkö, Okko T.; Lumela, Miikka; Rummukainen, Jaana; Nerg, Ossi; Seppälä, Toni T.; Herukka, Sanna-Kaisa; Koivisto, Anne M.; Alafuzoff, Irina; Puli, Lakshman; Savolainen, Sakari; Soininen, Hilkka; Jääskeläinen, Juha E.; Hiltunen, Mikko; Zetterberg, Henrik; Leinonen, Ville; Fiandaca, Massimo S. (17 March 2014). "Cerebrospinal Fluid Biomarker and Brain Biopsy Findings in Idiopathic Normal Pressure Hydrocephalus". PLoS ONE. 9 (3): e91974. Bibcode:2014PLoSO...991974P. doi:10.1371/journal.pone.0091974. PMC 3956805. PMID 24638077.
  9. Mouliere F, Mair R, Chandrananda D, Marass F, Smith CG, Su J, Morris J, Watts C, Brindle KM, Rosenfeld N (2018). "Detection of cell-free DNA fragmentation and copy number alterations in cerebrospinal fluid from glioma patients". EMBO Mol Med. 10 (12): e9323. doi:10.15252/emmm.201809323. PMC 6284385. PMID 30401727.CS1 maint: multiple names: authors list (link)
  10. "What is circulating tumor DNA and how is it used to diagnose and manage cancer? ". National Institutes of Health Genetics Home Reference. 5 March 2019. Retrieved 12 March 2019.
  11. "Liquid Biopsies Show High Correlation with Tissue Biopsy for Genetic Mutations". Oncology Practice Management. July 2016. Retrieved 12 March 2019.
  12. Picher, Andy."Liquid Biopsy, Key for Precision Medicine". Genetic Engineering & Biotechnology News. 23 July 2018. Retrieved 12 March 2019.
  13. "Liquid Biopsy: Differences Among Technologies". OncLive. 17 September 2017. Retrieved 12 March 2019.
  14. Ellis, Jen."dPCR: The Emergence of the Digital Age". Biocompare. 7 May 2018. Retrieved 12 March 2019.
  15. van der Pol Y, Mouliere F (2019). "Toward the early detection of cancer by decoding the epigenetic and environmental fingerprints of cell-free DNA". Cancer Cell. 36 (4): 350–368. doi:10.1016/j.ccell.2019.09.003. PMID 31614115.
  16. McDowell, Sandy."Liquid Biopsies: Past, Present, and Future". American Cancer Society. 12 February 2018. Retrieved 12 March 2019.
  17. "Liquid Biopsy: Using DNA in Blood to Detect, Track, and Treat Cancer". National Cancer Institute. 8 November 2017. Retrieved 12 March 2019.
  18. Olsson, Eleonor; Winter, Christof (2015). "Serial monitoring of circulating tumor DNA in patients with primary breast cancer for detection of occult metastatic disease". EMBO Molecular Medicine. 7 (8): 1034–1047. doi:10.15252/emmm.201404913. PMC 4551342. PMID 25987569.
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