title: Molecular-targeted therapies: lessons from years of clinical development.
abstract: Over the past decade, molecular-targeted therapies have been added to cytotoxic and anti-endocrine drugs in the treatment of cancer, with the aim to target the molecular pathways that underlie the carcinogenic process and maintain the cancer phenotype. Success with some of these agents has suggested that identification and validation of the drug target is the starting point for the route of development of active, safe and effective drugs. Main molecular targets used to the development of anticancer drugs are cell surface receptors, signal transduction pathways, gene transcription targets, ubiquitin-proteasome/heat shock proteins and tumour microenvironment components (especially antiangiogenic agents). Here, we review the development of the main molecular targeted non-cytotoxic agents studied in cancer, highlighting lessons derived from the development of these novel drugs and proposing new horizons for the clinical development of molecular-targeted therapies.
authors.affiliation: Medical Oncology Clinic, Jules Bordet Institute, and L Universite Libre de Bruxelles (ULB), Brussels, Belgium. dornellesrosa@hotmail.com
authors.forename: Daniela D
authors.initials: DD
authors.lastname: Rosa
authors.forename: Gustavo
authors.initials: G
authors.lastname: Ismael
authors.forename: Lissandra Dal
authors.initials: LD
authors.lastname: Lago
authors.forename: Ahmad
authors.initials: A
authors.lastname: Awada
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D016503:Drug Delivery Systems; D015195:Drug Design; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy*; D014411:Neoplastic Stem Cells / Q000637:transplantation; D015398:Signal Transduction