title: Drug-biomarker co-development in oncology - 20 years and counting.
abstract: Predictive biomarkers for oncology are necessary to accurately identify patients who will benefit from anticancer treatment. Recently approved oncology drugs target discrete molecular aberrations or pathways in tumor cells and consequently are active on a subset of patient population, yet clinical studies have shown that not all biomarker-positive patients respond. The advancement of predictive biomarkers needs to detect novel and evolving drug resistance mechanisms, not only to guide the selection of patient subsets for specific treatments, but to identify new therapeutic targets. Going beyond the "one marker, one drug" model to incorporate genomics, transcriptomics, and receptor status assessments during biomarker-drug co-development can aid in the successful application of molecular marker-based cancer therapy. This review provides the latest update of biomarker-based cancer therapeutics approved by the US Food and Drug Administration. We provide case studies of therapeutics selectively targeting HER2, EGFR, or PD-1/PD-L1 signaling pathways. We also discuss the challenges and promising future directions in the co-development of targeted cancer therapeutics and paired predictive biomarkers.
authors.affiliation: Office of Biotechnology Products, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, United States.
authors.forename: Julianne D
authors.initials: JD
authors.lastname: Twomey
authors.affiliation: Office of Biotechnology Products, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, United States.
authors.forename: Nina N
authors.initials: NN
authors.lastname: Brahme
authors.affiliation: Office of Biotechnology Products, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, United States. Electronic address: Baolin.Zhang@fda.hhs.gov.
authors.forename: Baolin
authors.initials: B
authors.lastname: Zhang
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D060890:B7-H1 Antigen / Q000187:drug effects; D014408:Biomarkers, Tumor / Q000032:analysis*; D066246:ErbB Receptors / Q000187:drug effects; D020869:Gene Expression Profiling; D006801:Humans; D008495:Medical Oncology / Q000379:methods*; D058990:Molecular Targeted Therapy / Q000379:methods*; D009369:Neoplasms / Q000188:drug therapy*; D057285:Precision Medicine / Q000379:methods*; D061026:Programmed Cell Death 1 Receptor / Q000187:drug effects; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000187:drug effects; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000970:Antineoplastic Agents; D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D061026:Programmed Cell Death 1 Receptor; D018719:Erb-b2 Receptor Tyrosine Kinases; C423236:CD274 protein, human; C105992:PDCD1 protein, human; C512478:EGFR protein, human; C508053:ERBB2 protein, human
keywords: Co-development; Companion diagnostics; Predictive biomarker; Targeted cancer therapy; Tumor heterogeneity