Patient selection is central to the success of targeted therapy; identification of tumour-specific molecular landscapes is pivotal to guiding treatment choices
The genomic landscape of each individual tumour is heterogeneous and changes over time as a result of the Darwinian clonal evolution imposed on cancer cells by selective pressures, including targeted therapy
Longitudinal surveillance of clonal evolution is essential for precision medicine, but cannot be effectively achieved using tissue biopsy specimens, owing to sampling issues
The blood of patients with cancer contains diverse tumour-derived materials, including circulating cell-free tumour DNA (ctDNA), circulating tumour cells, and exosomes
The sampling and analysis of ctDNA or other circulating tumour components present in biological fluids, termed 'liquid biopsy', enables minimally invasive monitoring of tumour evolution over time in the clinic
Two different liquid biopsy companion diagnostic tests for EGFR mutations in plasma ctDNA have been approved by the regulatory agencies in Europe and the USA for the selection of patients with non-small-cell lung cancer for anti-EGFR treatment in clinical practice
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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We thank Elizabeth Cook, a US-based freelancer graphic artist, for her assistance in drafting the figures for this article, and Beth Van Emburgh and Cosimo Martino of the Candiolo Cancer Institute for their assistance in revising the text. The work of the G.S. and A.B. is supported by the European Community's Seventh Framework Programme under grant agreement no. 602901 MErCuRIC, grant agreement no. 635342–2 MoTriColor, and IMI contract n. 115749 CANCER-ID; AIRC (Associazione Italiana per la Ricerca sul Cancro) 2010 Special Programme Molecular Clinical Oncology 5 per mille, project no. 9970; Fondazione Piemontese per la Ricerca sul Cancro-ONLUS 5 per mille 2010 e 2011 Ministero della Salute; and AIRC Investigator Grants project 16788.
G.S. is a consultant for Trovagene. A.B. is a member of the scientific advisory board for Biocartis, Horizon Discovery, and Trovagene. S.M. and S.S. declare no competing interests.
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Siravegna, G., Marsoni, S., Siena, S. et al. Integrating liquid biopsies into the management of cancer. Nat Rev Clin Oncol 14, 531–548 (2017). https://doi.org/10.1038/nrclinonc.2017.14
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