title: Multi-targeted tyrosine kinase inhibitors in clinical development: focus on XL-184 (cabozantinib).
abstract: XL-184 (cabozantinib) is a novel, small-molecule, multitargeted receptor tyrosine kinase inhibitor with particular activity against hepatocyte growth factor receptor (tyrosine-protein kinase Met), vascular endothelial growth factor receptor 2 (VEGFR-2) and proto-oncogene tyrosine-protein kinase receptor Ret. There is ample evidence of Met, VEGFR-2 and Ret signaling in several tumor types. Preclinical data suggest that XL-184 has activity in tumors derived from both epithelial and mesenchymal origins. Phase I and II clinical studies support significant antitumor activity, particularly in medullary thyroid cancer and cancers metastatic to the bone. This review will evaluate XL-184's preclinical pharmacology, pharmacokinetics, drug interactions and clinical activity in phase I through phase III studies.
authors.affiliation: University of Colorado Denver, Division of Medical Oncology, Aurora, Colorado 80045, USA.
authors.forename: D W
authors.initials: DW
authors.lastname: Bowles
authors.forename: E R
authors.initials: ER
authors.lastname: Kessler
authors.forename: A
authors.initials: A
authors.lastname: Jimeno
mesh_terms: D000813:Anilides / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004347:Drug Interactions; D015507:Drugs, Investigational / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D000090063:Proto-Oncogene Mas; D011725:Pyridines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*
chemical_list: D000813:Anilides; D000970:Antineoplastic Agents; D015507:Drugs, Investigational; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011725:Pyridines; C558660:cabozantinib; D020794:Receptor Protein-Tyrosine Kinases