title: Integrating liquid biopsies into the management of cancer.
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.
authors.affiliation: Candiolo Cancer Institute - Fondazione del Piemonte per l'Oncologia (FPO), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Strada Provinciale 142, Km 3.95, 10060 Candiolo, Torino, Italy.|Fondazione Italiana per la Ricerca sul Cancro (FIRC) Institute of Molecular Oncology (IFOM), Via Adamello 16, 20139 Milano, Italy.|Department of Oncology, University of Turin, Regione Gonzole 10, 10043 Orbassano, Torino, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Siravegna
authors.affiliation: Candiolo Cancer Institute - Fondazione del Piemonte per l'Oncologia (FPO), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Strada Provinciale 142, Km 3.95, 10060 Candiolo, Torino, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Marsoni
authors.affiliation: Niguarda Cancer Center, ASST Grande Ospedale Metropolitano Niguarda, Piazza dell'Ospedale Maggiore 3, 20162 Milano, Italy.|Department of Oncology and Haematology-Oncology, University of Milan, Via Festa del Perdono 7, 20122 Milano, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Siena
authors.affiliation: Candiolo Cancer Institute - Fondazione del Piemonte per l'Oncologia (FPO), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Strada Provinciale 142, Km 3.95, 10060 Candiolo, Torino, Italy.|Department of Oncology, University of Turin, Regione Gonzole 10, 10043 Orbassano, Torino, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Bardelli
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy / Q000379:methods*; D001800:Blood Specimen Collection / Q000379:methods; D004273:DNA, Neoplasm / Q000032:analysis; D019468:Disease Management; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000473:pathology; D009360:Neoplastic Cells, Circulating / Q000378:metabolism / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm