title: Prioritizing targets for precision cancer medicine.
abstract: The implementation of cancer genomic testing into the clinical setting has brought major opportunities. However, as our understanding of cancer initiation, maintenance and progression improves through detailed cancer genomic studies, the challenges associated with driver identification and target classification in the clinical setting become clearer. Here, we review recent insights into cancer genomic testing in the clinical setting, and suggest a target classification approach that considers the levels of evidence supporting the prioritization of tumour drivers for therapeutic targeting in light of complex cancer clonal and sub-clonal structures and clinical successes and failures in the field. We argue that such classification approaches, together with transparent reporting of both positive and negative clinical data and continued research to identify the sub-clonal dynamics of driver events during the disease course, will facilitate inter-trial comparisons, optimize patient informed consent and provide a critically balanced evaluation of genomic testing in clinical practice.
authors.affiliation: Department of Medical Oncology, INSERM U981, Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: F
authors.initials: F
authors.lastname: Andre
authors.affiliation: The Genome Institute, Washington University School of Medicine, St Louis, USA.
authors.forename: E
authors.initials: E
authors.lastname: Mardis
authors.affiliation: Cancer Research UK London Research Institute, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Salm
authors.affiliation: DITEP, Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: J-C
authors.initials: JC
authors.lastname: Soria
authors.affiliation: Princess Margaret Cancer Centre, Toronto, Canada.
authors.forename: L L
authors.initials: LL
authors.lastname: Siu
authors.affiliation: Cancer Research UK London Research Institute, London, UK; UCL Hospitals and Cancer Institute, Huntley Street, London, UK. Electronic address: charles.swanton@cancer.org.uk.
authors.forename: C
authors.initials: C
authors.lastname: Swanton
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D015894:Genome, Human; D006292:Health Priorities; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D012107:Research Design
chemical_list: D000970:Antineoplastic Agents
keywords: biomarkers; breast cancer; genomic instability; lung cancer