title: The next step: innovative molecular targeted therapies for treatment of intracranial chordoma patients.
abstract: BACKGROUND
  Chordomas are rare, locally aggressive malignancies that often exhibit an insidious natural history and are difficult to eradicate. Surgery and radiotherapy are the treatment mainstays of chordoma, but the chance of local recurrence remains high. Patients who relapse or cannot undergo a complete en bloc resection generally have a poor prognosis. New agents for postoperative adjuvant treatment of chordomas are needed.
  
  
  OBJECTIVE
  To highlight potential clinical trials that could evolve from new insights into the molecular biology of chordoma.
  
  
  METHODS
  We performed a review of recent studies published in the literature that have begun to characterize the molecular features of chordoma, and with this knowledge, several targets for potential clinical therapies have been determined.
  
  
  RESULTS
  Several receptor tyrosine kinases and their downstream signaling cascades show dysregulation in chordoma and represent attractive targets for future therapeutic interventions. The pathways shown to be of particular importance in chordoma involve the platelet-derived growth factor receptor, epidermal growth factor receptor, hepatocyte growth factor receptor, and common downstream cascade of phosphoinositide 3-kinases, Akt, and mammalian target of rapamycin.
  
  
  CONCLUSIONS
  Recent findings characterizing the molecular biology of chordoma have illuminated multiple possible targets for future clinical trials. The availability of inhibitors against these aberrant pathways makes clinical trials with chordoma both feasible and immediately realizable. Additionally, we emphasize the rationale for combination therapy when implementing molecular therapy in chordoma and other cancers.
authors.affiliation: Department of Neurological Surgery, University of California at San Francisco, San Francisco, California 94117, USA.
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Barry
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Jian
authors.forename: Michael E
authors.initials: ME
authors.lastname: Sughrue
authors.forename: Ari J
authors.initials: AJ
authors.lastname: Kane
authors.forename: Steven A
authors.initials: SA
authors.lastname: Mills
authors.forename: Tarik
authors.initials: T
authors.lastname: Tihan
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Parsa
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D002817:Chordoma / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D002986:Clinical Trials as Topic; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods / Q000639:trends*
chemical_list: D000970:Antineoplastic Agents