title: XL184 (cabozantinib) for medullary thyroid carcinoma.
abstract: BACKGROUND
  Intrathyroidal medullary thyroid carcinoma (MTC) can generally be cured by surgery, but distant metastases are often already present at diagnosis.Currently, there is no effective treatment for metastatic MTC. In these cases, consensus treatment guidelines explicitly recommend new experimental drugs. Several kinase inhibitors are now being tested for treatment of MTC in clinical trials and XL184, an oral, small-molecule multi-kinase inhibitor, seems to be one of the most promising of these compounds.
  
  
  METHODS
  We review preliminary data on the safety and efficacy of XL184 in metastatic MTC based on an extensive search of the literature, which included published articles, abstracts and website information. In particular,the review focuses on the rationale for using XL184 in advanced MTC. The compound has been specifically designed to target multiple signaling pathways,and this is expected to produce synergistic antitumor effects superior to those achieved by single-kinase inhibition. Preliminary results from the Phase I study of XL184 seem to support this hypothesis.
  
  
  CONCLUSIONS
  Multiple receptor tyrosine kinases (RTKs) are concomitantly activated in the same tumor. The blockade of a single RTK may engage compensatory signaling that maintains cell growth. Targeting multiple kinases might overcome both intrinsic and acquired resistance to antitumoral drugs.
authors.affiliation: University of Rome Sapienza, Department of Internal Medicine and Clinical Specialities, Viale del Policlinico 155, Rome, Italy.
authors.forename: Cosimo
authors.initials: C
authors.lastname: Durante
authors.forename: Diego
authors.initials: D
authors.lastname: Russo
authors.forename: Antonella
authors.initials: A
authors.lastname: Verrienti
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Filetti
mesh_terms: D000813:Anilides / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D018276:Carcinoma, Medullary / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018278:Carcinoma, Neuroendocrine; D002986:Clinical Trials as Topic; D006801:Humans; D009362:Neoplasm Metastasis; D047428:Protein Kinase Inhibitors / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use*; D011725:Pyridines / Q000494:pharmacology* / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects; D013964:Thyroid Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology
chemical_list: D000813:Anilides; D047428:Protein Kinase Inhibitors; D011725:Pyridines; C558660:cabozantinib