title: [Targeted therapy for locally advanced and/or metastatic bladder cancer].
abstract: Cancer is a complex disease characterized by a multitude of molecular and genetic abnormalities affecting cell proliferation and differentiation, apoptosis, and mobility (invasion). Each of these alterations represents a potential target for the development of targeted therapy. These new therapies inhibit cell growth and are said to be "cytostatic" in contrast with conventional "cytotoxic" chemotherapy. As a result of a better understanding of the molecular biology of bladder cancers, various signalling pathways involved in both carcinogenesis and tumour progression have been defined, and some of the key molecules in these pathways have been isolated and can be used as prognostic markers and as potential therapeutic targets. Locally advanced, and/or metastatic bladder cancer, is characterized by mutations of the p53 and retinoblastoma (Rb) genes, regulators of the cell cycle, which interact with the Ras-mitogen activated protein kinase (MPAK) transduction pathway. Overexpression of tyrosine kinase receptors, including EGFR, VEFGR and HER2/neu, is correlated with tumour progression and activation of the phosphatidyl-inositol-3 kinase (PI-3K) pathway is involved in tumour invasion and inhibition of apoptosis. Due to their molecular heterogeneity, optimal targeted therapy of bladder cancers will require the combined use of several molecules. Modulation of signalling pathways by these new molecules can restore chemosensitivity to cytotoxic drugs, which can then be associated with targeted therapy.
authors.affiliation: Service d'Urologie, CHU Pellegrin la Tripode, Université Bordeaux-II Victor-Segalen, Place Amélie-Raba-Léon, Bordeaux, France. herve.wallerand@chu-bordeaux.fr
authors.forename: H
authors.initials: H
authors.lastname: Wallerand
authors.forename: G
authors.initials: G
authors.lastname: Robert
authors.forename: J-C
authors.initials: JC
authors.lastname: Bernhard
authors.forename: A
authors.initials: A
authors.lastname: Ravaud
authors.forename: J-M
authors.initials: JM
authors.lastname: Ferrière
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000068258:Bevacizumab; D018450:Disease Progression; D000069347:Erlotinib Hydrochloride; D000077156:Gefitinib; D015316:Genetic Therapy; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D009154:Mutation; D010880:Piperidines / Q000008:administration & dosage / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D011725:Pyridines / Q000008:administration & dosage / Q000627:therapeutic use; D011799:Quinazolines / Q000008:administration & dosage / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D015398:Signal Transduction; D020123:Sirolimus / Q000008:administration & dosage / Q000627:therapeutic use; D052416:Targeted Gene Repair; D000068878:Trastuzumab; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000556:secondary; D003986:Dibenzocycloheptenes
chemical_list: D020533:Angiogenesis Inhibitors; D000903:Antibiotics, Antineoplastic; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000068258:Bevacizumab; D000069347:Erlotinib Hydrochloride; D000077156:Gefitinib; D007166:Immunosuppressive Agents; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D011799:Quinazolines; D020123:Sirolimus; D000068878:Trastuzumab; C115354:lonafarnib; D003986:Dibenzocycloheptenes