title: The Evolution of Oncology Companion Diagnostics from Signal Transduction to Immuno-Oncology.
abstract: Sixteen oncology drugs have been approved with a companion diagnostic (CDx) test by the FDA. These represent only 9.6% of the 167 oncology drug approvals since 1998, the year the first CDx test for Herceptin was approved. The great majority of CDx tests are for drugs that inhibit signal transduction pathways by either inhibiting the intracellular kinase activity with a small molecule or preventing ligand-induced receptor activation with a monoclonal antibody. In most of these cases, prospective patient selection for the biomarker-positive subpopulation was initiated in or before Phase II. The development of CDx tests for emerging immunotherapies will be more complicated because they are not dependent on driver mutations in the drug target, the mechanism of action is often pleiotropic, and will require both protein and cell-based assays to evaluate the interaction of the tumor with the immune system. Consequently, we will need to develop new biomarker strategies for the development of immunotherapies and to determine whether the optimum strategy is to release a prior checkpoint blockade in patients with a suppressed immune response, or to prime a new immune response to the tumor.
authors: Janssen Research & Development, 1400 McKean Road, Spring House, PA 19477, USA. Electronic address: ndracopo@its.jnj.com.
authors: Nicholas C
authors: NC
authors: Dracopoli
authors: Precision Medicine Network Inc., 1620 Sudbury Road, Concord, MA 01742, USA. Electronic address: mark.boguski@precisionready.com.
authors: Mark S
authors: MS
authors: Boguski
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000032:analysis; D003955:Diagnostic Tests, Routine; D006801:Humans; D007167:Immunotherapy; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D047428:Protein Kinase Inhibitors
keywords: immunotherapy; precision medicine; predictive biomarkers; signal transduction inhibitors