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Integrating liquid biopsies into the management of cancer. ​

Literature Information ​

DOI10.1038/nrclinonc.2017.14
PMID28252003
JournalNature reviews. Clinical oncology
Impact Factor82.2
JCR QuartileQ1
Publication Year2017
Times Cited906
Keywordsliquid biopsy, circulating tumor DNA, tumor heterogeneity, drug resistance, clinical oncology
Literature TypeJournal Article, Review
ISSN1759-4774
Pages531-548
Issue14(9)
AuthorsGiulia Siravegna, Silvia Marsoni, Salvatore Siena, Alberto Bardelli

TL;DR ​

This review highlights the potential of liquid biopsies, particularly circulating cell-free tumor DNA (ctDNA), as a more accurate and dynamic approach for profiling solid tumors compared to traditional tissue biopsies, which are limited by sampling bias and static snapshots of tumor heterogeneity. By integrating ctDNA analysis with other circulating biomarkers, this method can enhance monitoring of treatment responses, emergence of drug resistance, and management of minimal residual disease, ultimately improving patient care in oncology.

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liquid biopsy · circulating tumor DNA · tumor heterogeneity · drug resistance · clinical oncology

Abstract ​

During cancer progression and treatment, multiple subclonal populations of tumour cells compete with one another, with selective pressures leading to the emergence of predominant subclones that replicate and spread most proficiently, and are least susceptible to treatment. At present, the molecular landscapes of solid tumours are established using surgical or biopsy tissue samples. Tissue-based tumour profiles are, however, subject to sampling bias, provide only a snapshot of tumour heterogeneity, and cannot be obtained repeatedly. Genomic profiles of circulating cell-free tumour DNA (ctDNA) have been shown to closely match those of the corresponding tumours, with important implications for both molecular pathology and clinical oncology. Analyses of circulating nucleic acids, commonly referred to as 'liquid biopsies', can be used to monitor response to treatment, assess the emergence of drug resistance, and quantify minimal residual disease. In addition to blood, several other body fluids, such as urine, saliva, pleural effusions, and cerebrospinal fluid, can contain tumour-derived genetic information. The molecular profiles gathered from ctDNA can be further complemented with those obtained through analysis of circulating tumour cells (CTCs), as well as RNA, proteins, and lipids contained within vesicles, such as exosomes. In this Review, we examine how different forms of liquid biopsies can be exploited to guide patient care and should ultimately be integrated into clinical practice, focusing on liquid biopsy of ctDNA - arguably the most clinically advanced approach.

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Primary Questions Addressed ​

  1. How can the integration of liquid biopsies improve the early detection of cancer compared to traditional methods?
  2. What are the challenges and limitations in implementing liquid biopsies in routine clinical practice for cancer management?
  3. In what ways can liquid biopsies contribute to personalized medicine approaches in oncology?
  4. How do the molecular profiles obtained from liquid biopsies compare to those from traditional tissue biopsies in terms of accuracy and reliability?
  5. What future advancements in liquid biopsy technology could further enhance its role in cancer treatment monitoring and resistance detection?

Key Findings ​

Key Insights ​

  1. Background and Objectives: The study addresses the limitations of conventional tissue sampling in cancer management, which often leads to incomplete understanding of tumor heterogeneity and dynamics. Tumors consist of diverse subclonal populations that evolve under selective pressures during progression and treatment. The primary objective of the research is to explore the integration of liquid biopsies, particularly circulating tumor DNA (ctDNA), into cancer management to enhance monitoring and treatment strategies.

  2. Main Methods and Findings: The review discusses various types of liquid biopsies, including ctDNA, circulating tumor cells (CTCs), and genetic materials from other body fluids such as urine, saliva, and cerebrospinal fluid. It highlights that ctDNA provides a genomic profile that closely resembles that of the primary tumor, allowing for real-time monitoring of tumor evolution. The findings emphasize that liquid biopsies can effectively assess treatment responses, track the emergence of drug resistance, and quantify minimal residual disease (MRD). The integration of diverse liquid biopsy methodologies can potentially offer a comprehensive view of tumor dynamics that is not achievable through traditional tissue biopsies alone.

  3. Core Conclusions: The review concludes that liquid biopsy techniques, especially ctDNA analysis, represent a significant advancement in the management of cancer. They offer a non-invasive way to capture the genetic landscape of tumors and to monitor changes over time, which is crucial for personalized treatment approaches. The authors advocate for the incorporation of liquid biopsies into routine clinical practice to improve patient care and outcomes.

  4. Research Significance and Impact: The integration of liquid biopsies into cancer management holds transformative potential for oncology. By providing a more dynamic and comprehensive understanding of tumor biology, these methodologies can lead to more accurate prognoses, tailored treatment regimens, and better management of drug resistance. The implications of this research extend beyond individual patient care; they suggest a paradigm shift in how cancer is monitored and treated, paving the way for more effective and individualized therapeutic strategies. As liquid biopsies become more mainstream, they could significantly enhance our ability to combat cancer and improve survival rates.

References ​

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Literatures Citing This Work ​

  1. Implementing liquid biopsies into clinical decision making for cancer immunotherapy. - Dagmar Quandt;Hans Dieter Zucht;Arno Amann;Anne Wulf-Goldenberg;Carl Borrebaeck;Michael Cannarile;Diether Lambrechts;Herbert Oberacher;James Garrett;Tapan Nayak;Michael Kazinski;Charles Massie;Heidi Schwarzenbach;Michele Maio;Robert Prins;Björn Wendik;Richard Hockett;Daniel Enderle;Mikkel Noerholm;Hans Hendriks;Heinz Zwierzina;Barbara Seliger - Oncotarget (2017)
  2. What We Know About Stage II and III Colon Cancer: It's Still Not Enough. - Alberto Puccini;Martin D Berger;Wu Zhang;Heinz-Josef Lenz - Targeted oncology (2017)
  3. Early phase clinical trials of anticancer agents in children and adolescents - an ITCC perspective. - Lucas Moreno;Andrew D J Pearson;Xavier Paoletti;Irene Jimenez;Birgit Geoerger;Pamela R Kearns;C Michel Zwaan;Francois Doz;Andre Baruchel;Josef Vormoor;Michela Casanova;Stefan M Pfister;Bruce Morland;Gilles Vassal; - Nature reviews. Clinical oncology (2017)
  4. Salivary exosomal PSMA7: a promising biomarker of inflammatory bowel disease. - Xiaowen Zheng;Feng Chen;Qian Zhang;Yulan Liu;Peng You;Shan Sun;Jiuxiang Lin;Ning Chen - Protein & cell (2017)
  5. Medical research: Personalized test tracks cancer relapse. - Alberto Bardelli - Nature (2017)
  6. Changes of Microrna Levels in Plasma of Patients with Rectal Cancer during Chemoradiotherapy. - Peter Jo;Azadeh Azizian;Junius Salendo;Frank Kramer;Markus Bernhardt;Hendrik A Wolff;Jens Gruber;Marian Grade;Tim Beißbarth;B Michael Ghadimi;Jochen Gaedcke - International journal of molecular sciences (2017)
  7. Extracellular Vesicles in Hematological Malignancies: From Biology to Therapy. - Antonella Caivano;Francesco La Rocca;Ilaria Laurenzana;Stefania Trino;Luciana De Luca;Daniela Lamorte;Luigi Del Vecchio;Pellegrino Musto - International journal of molecular sciences (2017)
  8. Optofluidic device for the quantification of circulating tumor cells in breast cancer. - Eric Pedrol;Manuel Garcia-Algar;Jaume Massons;Moritz Nazarenus;Luca Guerrini;Javier Martínez;Airan Rodenas;Ana Fernandez-Carrascal;Magdalena Aguiló;Laura G Estevez;Isabel Calvo;Ana Olano-Daza;Eduardo Garcia-Rico;Francesc Díaz;Ramon A Alvarez-Puebla - Scientific reports (2017)
  9. Prostate Cancer Stem Cell Markers Drive Progression, Therapeutic Resistance, and Bone Metastasis. - Koran S Harris;Bethany A Kerr - Stem cells international (2017)
  10. The past and future of breast cancer treatment-from the papyrus to individualised treatment approaches. - Felipe Ades;Konstantinos Tryfonidis;Dimitrios Zardavas - Ecancermedicalscience (2017)

... (896 more literatures)

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