title: Targeting fibroblast growth factor receptors and immune checkpoint inhibitors for the treatment of advanced bladder cancer: New direction and New Hope.
abstract: Bladder cancer is one of the leading causes of death in Europe and the United States. About 25% of patients with bladder cancer have advanced disease (muscle-invasive or metastatic disease) at presentation and are candidates for systemic chemotherapy. In the setting of metastatic disease, use of cisplatin-based regimens improves survival. However, despite initial high response rates, the responses are typically not durable leading to recurrence and death in the vast majority of these patients with median overall survival of 15months and a 5-year survival rate of ⩽10%. Furthermore, unfit patients for cisplatin have no standard of care for first line therapy in advance disease Most second-line chemotherapeutic agents tested have been disappointing. Newer targeted drugs and immunotherapies are being studied in the metastatic setting, their usefulness in the neoadjuvant and adjuvant settings is also an intriguing area of ongoing research. Thus, new treatment strategies are clearly needed. The comprehensive evaluation of multiple molecular pathways characterized by The Cancer Genome Atlas project has shed light on potential therapeutic targets for bladder urothelial carcinomas. We have focused especially on emerging therapies in locally advanced and metastatic urothelial carcinoma with an emphasis on immune checkpoints inhibitors and FGFR targeted therapies, which have shown great promise in early clinical studies.
authors.affiliation: Vall d'Hebron Institute of Oncology, Vall d' Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Morales-Barrera
authors.affiliation: Vall d'Hebron Institute of Oncology, Vall d' Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Suárez
authors.affiliation: Vall d'Hebron Institute of Oncology, Vall d' Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Ana Martínez
authors.initials: AM
authors.lastname: de Castro
authors.affiliation: Vall d'Hebron Institute of Oncology, Vall d' Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Fabricio
authors.initials: F
authors.lastname: Racca
authors.affiliation: Vall d'Hebron Institute of Oncology, Vall d' Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Claudia
authors.initials: C
authors.lastname: Valverde
authors.affiliation: Department of Radiation Oncology, Vall d' Hebron University Hospital, Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Maldonado
authors.affiliation: Department of Urology, Vall d' Hebron University Hospital, Barcelona, Spain.
authors.forename: Juan Maria
authors.initials: JM
authors.lastname: Bastaros
authors.affiliation: Department of Urology, Vall d' Hebron University Hospital, Barcelona, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Morote
authors.affiliation: Vall d'Hebron Institute of Oncology, Vall d' Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain. Electronic address: jcarles@vhio.net.
authors.forename: Joan
authors.initials: J
authors.lastname: Carles
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D000074324:Ipilimumab; D000077594:Nivolumab; D010671:Phenylurea Compounds / Q000627:therapeutic use; D010879:Piperazines / Q000627:therapeutic use; D011720:Pyrazoles / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use; D011804:Quinolines / Q000627:therapeutic use; D011810:Quinoxalines / Q000627:therapeutic use; D017468:Receptors, Fibroblast Growth Factor / Q000037:antagonists & inhibitors*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000074324:Ipilimumab; D010671:Phenylurea Compounds; D010879:Piperazines; D011720:Pyrazoles; D011725:Pyridines; D011743:Pyrimidines; D011804:Quinolines; D011810:Quinoxalines; D017468:Receptors, Fibroblast Growth Factor; C000613593:durvalumab; D000077594:Nivolumab; C000594389:atezolizumab; C000604580:erdafitinib; C568950:infigratinib; C582435:pembrolizumab; C500026:palbociclib; C487932:neratinib; C000609138:avelumab
keywords: Anti-EGFR; Anti-angiogenesis; Cell cycle; FGFR targeted therapies; Immunotherapy; Targeting PI3K/AKT/mTOR pathway; Urothelial carcinoma