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Neurosurgery. 2011 Jan;68(1):231-40; discussion 240-1. doi: 10.1227/NEU.0b013e3181fd2ac5.

The next step: innovative molecular targeted therapies for treatment of intracranial chordoma patients.

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  • 1Department of Neurological Surgery, University of California at San Francisco, San Francisco, California 94117, USA.

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.

CONCLUSION:

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.

PMID:
21099719
[PubMed - indexed for MEDLINE]
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