title: [Nintedanib (BIBF 1120) in the treatment of solid cancers: an overview of biological and clinical aspects].
abstract: Angiogenesis is essential for tumor growth and metastasis. The main regulators of the process are the signaling cascades of VEGF-, PDGF- and FGF receptors. Inhibition of these pathways holds potential therapeutic benefit not only for cancer patients, but also for the treatment of other diseases. This paper summarizes the experimental and clinical results of studies available so far on the multi-target tyrosine kinase inhibitor nintedanib (BIBF 1120). According to these studies, nintedanib effectively inhibits VEGFR-, PDGFR- and FGFR signalization and thus the proliferation and survival of cell types which highly express these receptors (i.e. endothelial and smooth muscle cells and pericytes). In vitro studies and in vivo xenograft experiments have provided promising results. In the clinical setting, BIBF 1120 seems to be effective and well tolerated in various tumor types, such as lung, prostate, colorectal and hepatocellular carcinoma, as well as in gynecological tumors. The main adverse events are gastrointestinal toxicities and the reversible elevation of liver enzyme levels. Nintedanib might also be combined with paclitaxel, carboplatin, pemetrexed and docetaxel. There are several ongoing clinical trials testing the efficacy of BIBF 1120.
authors.affiliation: Tumorbiológiai Osztály, Országos Korányi TBC és Pulmonológiai Intézet, Budapest, Hungary. szilvia.torok@koranyi.hu
authors.forename: Szilvia
authors.initials: S
authors.lastname: Török
authors.forename: Mihály
authors.initials: M
authors.lastname: Cserepes T
authors.forename: Ferenc
authors.initials: F
authors.lastname: Rényi-Vámos
authors.forename: Balázs
authors.initials: B
authors.lastname: Döme
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000077784:Axitinib; D001557:Benzenesulfonates / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism; D002986:Clinical Trials as Topic; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000378:metabolism; D004064:Digestive System / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D005833:Genital Neoplasms, Female / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use; D007191:Indazoles / Q000627:therapeutic use; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D009536:Niacinamide / Q000031:analogs & derivatives / Q000627:therapeutic use; D009841:Oligonucleotides; D010671:Phenylurea Compounds; D010793:Phthalazines / Q000627:therapeutic use; D010880:Piperidines / Q000627:therapeutic use; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011725:Pyridines / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use; D011799:Quinazolines / Q000627:therapeutic use; D017468:Receptors, Fibroblast Growth Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000077157:Sorafenib; D013449:Sulfonamides / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D004791:Enzyme Inhibitors; D007093:Imidazoles; D007191:Indazoles; D007211:Indoles; D009841:Oligonucleotides; D010671:Phenylurea Compounds; D010793:Phthalazines; D010880:Piperidines; D011725:Pyridines; D011743:Pyrimidines; D011799:Quinazolines; D017468:Receptors, Fibroblast Growth Factor; D013449:Sulfonamides; D009536:Niacinamide; C404768:vatalanib; C516667:pazopanib; D000077157:Sorafenib; D000077784:Axitinib; D011505:Protein-Tyrosine Kinases; D017479:Receptors, Platelet-Derived Growth Factor; D040262:Receptors, Vascular Endothelial Growth Factor; C519562:imetelstat; C530716:nintedanib; C500926:cediranib; C452423:vandetanib