title: A place for precision medicine in bladder cancer: targeting the FGFRs.
abstract: Bladder tumors show diverse molecular features and clinical outcome. Muscle-invasive bladder cancer has poor prognosis and novel approaches to systemic therapy are urgently required. Non-muscle-invasive bladder cancer has good prognosis, but high recurrence rate and the requirement for life-long disease monitoring places a major burden on patients and healthcare providers. Studies of tumor tissues from both disease groups have identified frequent alterations of FGFRs, including mutations of FGFR3 and dysregulated expression of FGFR1 and FGFR3 that suggest that these may be valid therapeutic targets. We summarize current understanding of the molecular alterations affecting these receptors in bladder tumors, preclinical studies validating them as therapeutic targets, available FGFR-targeted agents and results from early clinical trials in bladder cancer patients.
authors.affiliation: Section of Molecular Oncology, Leeds Institute of Cancer & Pathology, St James's University Hospital, Beckett Street, Leeds, LS9 7TF, UK.
authors.forename: Erica
authors.initials: E
authors.lastname: di Martino
authors.affiliation: Astbury Centre for Structural & Molecular Biology, School of Molecular & Cellular Biology, Astbury Building, University of Leeds, Leeds, LS2 9JT, UK.
authors.forename: Darren C
authors.initials: DC
authors.lastname: Tomlinson
authors.affiliation: Section of Molecular Oncology, Leeds Institute of Cancer & Pathology, St James's University Hospital, Beckett Street, Leeds, LS9 7TF, UK.
authors.forename: Sarah V
authors.initials: SV
authors.lastname: Williams
authors.affiliation: Section of Molecular Oncology, Leeds Institute of Cancer & Pathology, St James's University Hospital, Beckett Street, Leeds, LS9 7TF, UK.
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Knowles
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015415:Biomarkers; D004353:Drug Evaluation, Preclinical; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008024:Ligands; D058990:Molecular Targeted Therapy; D009154:Mutation; D009367:Neoplasm Staging; D063868:Patient Outcome Assessment; D018579:Patient Selection; D057285:Precision Medicine / Q000379:methods; D011379:Prognosis; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics / Q000378:metabolism; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014178:Translocation, Genetic; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D008024:Ligands; D066246:ErbB Receptors; C496348:FGFR1 protein, human; C496365:FGFR3 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051498:Receptor, Fibroblast Growth Factor, Type 3
keywords: FGFR1; FGFR3; FGFRs; bladder; cancer; targeted therapy; urothelial