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„Liquid biopsy“ – schon reif für Therapieentscheidungen?

Liquid biopsy—ready to guide treatment decisions?

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best practice onkologie Aims and scope

Zusammenfassung

Flüssigbiopsien („liquid biopsy“, LB) ermöglichen die wenig invasive und wiederholbare Materialgewinnung von Tumorpatienten aus verschiedenen Körperflüssigkeiten wie beispielsweise dem Blut, Urin oder Liquor. Mithilfe der LB können dann intakte Tumorzellen oder Produkte von Tumorzellen wie RNA, DNA, extrazelluläre Vesikel oder Proteine untersucht werden. Die Möglichkeiten, die sich durch den Einsatz von LB-Methoden ergeben, beinhalten die Früherkennung, Risikostratifizierung, Therapiesteuerung und Rückfallerkennung von (soliden) Tumoren. Trotz des enormen Potenzials ist der Einsatz der LB derzeit auf klinische Studien und wenige zugelassene Tests begrenzt. Eine flächendeckende Implementierung der LB in die klinische Routine verspricht eine individuellere Tumortherapie mit verbesserten Detektions- und Überlebensraten. Im Folgenden präsentieren die Autoren einen Überblick über die häufigsten Methoden und stellen die derzeitige Studienlage kritisch dar. Ebenso werden potenzielle Hürden und Bemühungen auf dem Weg zur standardmäßigen klinischen Implementierung diskutiert.

Abstract

Liquid biopsy (LB)-based methods enable less invasive and repeatable sample collection from various body fluids of cancer patients including blood, urine, and cerebrospinal fluid. Samples retrieved by LB can be used to characterize intact tumor cells or tumor-associated products such as RNA, DNA, extracellular vesicles, and proteins. Applications of LB include early detection, risk stratification, treatment guidance, and detection of relapse of (solid) tumors. Despite its enormous potential, the use of LB is currently limited to clinical trials and a small number of approved tests. The implementation of LB in clinical practice promises a more personalized cancer treatment with improved detection and survival rates. In this article, the authors provide an overview of the most common LB methods and critically review the current study situation. Additionally, potential hurdles that must be overcome and efforts for clinical implementation are discussed.

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Abbreviations

cfDNA:

Zellfreie Desoxyribonukleinsäure, „cell-free deoxyribonucleic acid“

CNA:

Kopienzahlvariationen, „copy number aberrations“

CTC:

Zirkulierende Tumorzelle, „circulating tumor cell“

ctDNA:

Zirkulierende Tumor-Desoxyribonukleinsäure, „circulating tumor deoxyribonucleic acid“

ddPCR:

Digitale Tröpfchen-Polymerasekettenreaktion, „droplet digital polymerase chain reaction“

DELFI:

„DNA evaluation of fragments for early interception“

DNA:

Desoxyribonukleinsäure

dPCR:

Digitale Polymerasekettenreaktion, „digital polymerase chain reaction“

EGFR:

„Epidermal growth factor receptor“

ELBS:

European Liquid Biopsy Society

EU:

Europäische Union

EV:

Extrazelluläre Vesikel

FDA:

U.S. Food and Drug Administration

ILSA:

International Liquid Biopsy Standardization Alliance

KRAS:

„Kirsten rat sarcoma“

LB:

Flüssigbiopsie, Flüssigkeitsbiopsie, „liquid biopsy“

miRNA:

MicroRNA

MRD:

Minimale Resterkrankung, „minimal residual disease“

NGS:

Nächste-Generation-Sequenzierung, „next-generation sequencing“

NPW:

Negativer prädiktiver Wert

NSCLC:

Nichtkleinzelliges Lungenkarzinom, „non-small cell lung cancer“

PCR:

Polymerasekettenreaktion, „polymerase chain reaction“

PI3K:

Phosphoinositid-3-Kinase

PPW:

Positiver prädiktiver Wert

RECIST:

Response Evaluation Criteria In Solid Tumors

RNA:

Ribonukleinsäure, „ribonucleic acid“

RT-PCR:

Quantitative Echtzeit-Polymerasekettenreaktion, „real-time quantitative PCR“

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Förderung

N.S. erhielt finanzielle Unterstützung durch ein Else Kröner-Fresenius-Stiftung iPRIME Stipendium (2021_EKPK.10) im Rahmen ihrer Promotion am Universitätsklinikum Hamburg-Eppendorf. K.P. erhielt Forschungsförderung durch EU/IMI CANCER-ID EFPIA, ERC Advanced Investigator Grant INJURMET (Förderungsnummer: 834974), European Union Horizon 2020 Research and Innovation program (Marie Skłodowska-Curie grant agreement; Förderungsnummer: 765492), ERA-NET EU/TRANSCAN 2 JTC 2016 PROLIPSY, Deutsche Krebshilfe (Förderungsnummer: 70112504) und Deutsche Forschungsgemeinschaft (DFG) im Rahmen des Schwerpunktprogramms µBone (Nummer: SPP2084). K.P. und D.J.S. erhielten finanzielle Unterstützung durch die Hiege Stiftung – die Deutsche Hautkrebsstiftung im Rahmen der Gründung des Fleur Hiege-Centrum für Hautkrebsforschung am Universitätsklinikum Hamburg-Eppendorf.

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Authors and Affiliations

  1. Klinik und Poliklinik für Dermatologie und Venerologie, Fleur Hiege-Centrum für Hautkrebsforschung, Universitätsklinikum Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Deutschland

    Carmen M. T. Roeper, Inka Hoehne & Noemi Schlepper

  2. Institut für Tumorbiologie, Fleur Hiege-Centrum für Hautkrebsforschung, Universitätsklinikum Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Deutschland

    Carmen M. T. Roeper, Inka Hoehne, Noemi Schlepper,  Klaus Pantel &  Daniel J. Smit

  3. Institut für Tumorbiologie, European Liquid Biopsy Society (ELBS), Universitätsklinikum Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Deutschland

    Claudia Koch

  4. Institut für Tumorbiologie, Universitätsklinikum Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Deutschland

    Klaus Pantel &  Daniel J. Smit

Authors
  1. Carmen M. T. Roeper
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  2. Inka Hoehne
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  3. Noemi Schlepper
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  4. Claudia Koch
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  5. Klaus Pantel
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Corresponding authors

Correspondence to Klaus Pantel or Daniel J. Smit.

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Interessenkonflikt

K.P. erhielt Honorare von BMS, Agena, Menarini, Novartis, Sanofi, Illumina, Abcam, MSD, Boehringer Ingelheim, Eppendorf und Hummingbird. C.M.T. Roeper, I. Hoehne, N. Schlepper, C. Koch, K. Pantel und D.J. Smit geben an, dass kein Interessenkonflikt besteht.

Für diesen Beitrag wurden von den Autor/-innen keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

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Roeper, C.M.T., Hoehne, I., Schlepper, N. et al. „Liquid biopsy“ – schon reif für Therapieentscheidungen?. best practice onkologie 18, 194–202 (2023). https://doi.org/10.1007/s11654-023-00484-x

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