Liquid Biopsy – Ein neues diagnostisches Konzept in der Onkologie

Zusammenfassung

Die Analyse von im Blut zirkulierenden Tumorzellen oder von in anderen Körperflüssigkeiten zirkulierenden Tumorzellprodukten gewann in den letzten Jahren stetig an Aufmerksamkeit. Sie wird unter dem Begriff Flüssigbiopsie (Liquid Biopsy, LB) zusammengefasst. In diesem Beitrag werden die wichtigsten LB-Analyten vorgestellt sowie die noch bestehenden Hürden und vielfältigen Bemühungen der Implementierung der LB in die klinische Routine diskutiert.

Abstract

The analysis of tumor cells circulating in the blood or of products of tumor cells circulating in other body fluids has gained increasing attention in recent years and is summarized under the term liquid biopsy (LB). LB includes the analysis of circulating tumor cells, cell-free circulating tumor-associated nucleic acids, extracellular vesicles, proteins, or other products that are released into the peripheral bloodstream by the primary or metastatic tumor. For a huge number of solid tumor entities, LB has already been successfully applied in preclinical and clinical studies for the detection, risk stratification, treatment monitoring and relapse detection. LB provides valuable real-time information on tumor cell development, therapeutic targets, and mechanisms of therapy resistance using a non-invasive peripheral blood test. In this article, the most important LB analytes and the current state of research are presented. In addition, the remaining obstacles and the diverse efforts to implement LB in clinical routine are critically discussed.

Kernaussagen

• Liquid Biopsy bezeichnet die Analyse von Tumorzellen oder Tumorzellprodukten aus dem Blut und anderen Körperflüssigkeiten.

• Zu den Vorteilen der Liquid Biopsy gehören die minimalinvasive Durchführung, die Wiederholbarkeit und die Gewinnung von zusätzlichen patientenindividuellen Informationen über die Krebserkrankung.

• Die (potenziellen) Anwendungsgebiete der Liquid Biopsy umfassen die Früherkennung von Tumoren, die Risikostratifizierung, die Therapiewahl und Therapieüberwachung sowie die frühzeitige Erkennung von Rezidiven und minimalen Resterkrankungen.

• Verschiedenste Initiativen, wie beispielsweise die European Liquid Biopsy Society (ELBS) und die International Liquid Biopsy Standardization Alliance (ILSA), sind bemüht, Hürden für die klinische Implementierung der Liquid Biopsy abzubauen.

Schlüsselwörter

Liquid Biopsy - zirkulierende Tumor‐DNA - zirkulierende Tumorzellen - minimale Resterkrankung - Therapieüberwachung - zielgerichtete Therapien

Keywords

Liquid Biopsy - ctDNA - CTCs - MRD - therapeutic decision making - targeted therapy

Publikationsverlauf

Artikel online veröffentlicht:
25. September 2023

• Literatur

• 1 Bardelli A, Pantel K. Liquid biopsies, what we do not know (yet). Cancer Cell 2017; 31: 172-179
• 2 Sung H, Ferlay J, Siegel RL. et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021; 71: 209-249
• 3 Pantel K, Alix-Panabières C. Circulating tumour cells in cancer patients: challenges and perspectives. Trends Mol Med 2010; 16: 398-406
• 4 Alix-Panabières C, Pantel K. Liquid biopsy: From discovery to clinical application. Cancer Discov 2021; 11: 858-873
• 5 Cheng YH, Chen YC, Lin E. et al. Hydro-Seq enables contamination-free high-throughput single-cell RNA-sequencing for circulating tumor cells. Nat Commun 2019; 10: 2163
• 6 Pantel K, Alix-Panabieres C. Liquid biopsy and minimal residual disease – latest advances and implications for cure. Nat Rev Clin Oncol 2019; 16: 409-424
• 7 Smit DJ, Pantel K, Jücker M. Circulating tumor cells as a promising target for individualized drug susceptibility tests in cancer therapy. Biochem Pharmacol 2021; 188: 114589
• 8 Thierry AR, El Messaoudi S, Gahan PB. et al. Origins, structures, and functions of circulating DNA in oncology. Cancer Metastasis Rev 2016; 35: 347-376
• 9 Yu W, Hurley J, Roberts D. et al. Exosome-based liquid biopsies in cancer: opportunities and challenges. Ann Oncol 2021; 32: 466-477
• 10 Liu J, Jennings SF, Tong W. et al. Next generation sequencing for profiling expression of miRNAs: technical progress and applications in drug development. J Biomed Sci Eng 2011; 4: 666-676
• 11 Hoshino A, Kim HS, Bojmar L. et al. Extracellular vesicle and particle biomarkers define multiple human cancers. Cell 2020; 182: 1044-1061.e1018
• 12 Ding Z, Wang N, Ji N. et al. Proteomics technologies for cancer liquid biopsies. Mol Cancer 2022; 21: 53
• 13 Chen M, Zhao H. Next-generation sequencing in liquid biopsy: cancer screening and early detection. Hum Genomics 2019; 13: 34
• 14 Nicolazzo C, Barault L, Caponnetto S. et al. True conversions from RAS mutant to RAS wild-type in circulating tumor DNA from metastatic colorectal cancer patients as assessed by methylation and mutational signature. Cancer Lett 2021; 507: 89-96
• 15 Newman AM, Bratman SV, To J. et al. An ultrasensitive method for quantitating circulating tumor DNA with broad patient coverage. Nat Med 2014; 20: 548-554
• 16 Cohen JD, Li L, Wang Y. et al. Detection and localization of surgically resectable cancers with a multi-analyte blood test. Science (New York, NY) 2018; 359: 926-930
• 17 Liu MC, Oxnard GR, Klein EA. et al. Sensitive and specific multi-cancer detection and localization using methylation signatures in cell-free DNA. Ann Oncol 2020; 31: 745-759
• 18 Cristiano S, Leal A, Phallen J. et al. Genome-wide cell-free DNA fragmentation in patients with cancer. Nature 2019; 570: 385-389
• 19 Heidrich I, Ačkar L, Mossahebi Mohammadi P. et al. Liquid biopsies: Potential and challenges. Int J Cancer 2021; 148: 528-545
• 20 Bidard FC, Kiavue N, Ychou M. et al. Circulating tumor cells and circulating tumor DNA detection in potentially resectable metastatic colorectal cancer: a prospective ancillary study to the Unicancer Prodige-14 Trial. Cells 2019; 8: 516
• 21 Woodhouse R, Li M, Hughes J. et al. Clinical and analytical validation of FoundationOne Liquid CDx, a novel 324-Gene cfDNA-based comprehensive genomic profiling assay for cancers of solid tumor origin. PloS one 2020; 15: e0237802
• 22 Razavi P, Dickler MN, Shah PD. et al. Alterations in PTEN and ESR1 promote clinical resistance to alpelisib plus aromatase inhibitors. Nat Cancer 2020; 1: 382-393
• 23 Ignatiadis M, Sledge GW, Jeffrey SS. Liquid biopsy enters the clinic – implementation issues and future challenges. Nat Rev Clin Oncol 2021; 18: 297-312
• 24 Garcia-Murillas I, Chopra N, Comino-Méndez I. et al. Assessment of molecular relapse detection in early-stage breast cancer. JAMA Oncol 2019; 5: 1473-1478
• 25 Tie J, Wang Y, Tomasetti C. et al. Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer. Sci Transl Med 2016; 8: 346ra392
• 26 Trapp E, Janni W, Schindlbeck C. et al. Presence of circulating tumor cells in high-risk early breast cancer during follow-up and prognosis. J Natl Cancer Inst 2019; 111: 380-387
• 27 Connors D, Allen J, Alvarez JD. et al. International liquid biopsy standardization alliance white paper. Crit Rev Oncol Hematol 2020; 156: 103112