title: A framework for genomic biomarker actionability and its use in clinical decision making.
abstract: The increasing scope and availability of genetic testing options for patients suffering from cancer has raised questions about how to use results of molecular diagnostics to inform patient care. For some biomarkers (e.g. BRAF mutations in melanoma), standards exist that outline treatments for individuals harboring aberrations in the biomarker; however for the vast majority of genomic abnormalities, few guidelines exist. Clinical decision making and the therapeutic approach for a patient with a given cancer characterized by aberrations in different genes may be aided by the use of a biomarker actionability framework that provides levels of evidence regarding whether and how a molecular abnormality can be considered a therapeutically relevant biomarker. A gene may be considered theoretically actionable if it has a basis of actionability, such that clinically available drugs can target a gene product that drives the cancer or is differentially expressed in tumor versus normal elements. Herein, we discuss a possible framework for developing guidelines for actionability, as they relate to genomically-based cancer therapeutics.
authors.affiliation: CollabRx Inc., San Francisco, California, USA.
authors.forename: Smruti J
authors.initials: SJ
authors.lastname: Vidwans
authors.affiliation: CollabRx Inc., San Francisco, California, USA.
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Turski
authors.affiliation: Department of Investigational Cancer Therapeutics - a Phase I Clinical Trials Program, The University of Texas MD Anderson Cancer Center Houston, Texas, USA.
authors.forename: Filip
authors.initials: F
authors.lastname: Janku
authors.affiliation: Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, USA.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Garrido-Laguna
authors.affiliation: Banner MD Anderson Cancer Center, Gilbert, Arizona, USA.
authors.forename: Javier
authors.initials: J
authors.lastname: Munoz
authors.affiliation: Center for Personalized Cancer Therapy, Moores Cancer Center, University of California, San Diego, California, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Schwab
authors.affiliation: Department of Investigational Cancer Therapeutics - a Phase I Clinical Trials Program, The University of Texas MD Anderson Cancer Center Houston, Texas, USA.
authors.forename: Vivek
authors.initials: V
authors.lastname: Subbiah
authors.affiliation: Vall d'Hebron Institut d'Oncologia and Universitat Autonoma of Barcelona, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Rodon
authors.affiliation: Center for Personalized Cancer Therapy, Moores Cancer Center, University of California, San Diego, California, USA.
authors.forename: Razelle
authors.initials: R
authors.lastname: Kurzrock
keywords: Biomarker; Clinical decision making; Predictive biomarkers; Targeted therapies