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      Novel targeted therapies in chordoma: an update

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          Abstract

          Chordomas are rare, locally aggressive skull base neoplasms known for local recurrence and not-infrequent treatment failure. Current evidence supports the role of maximal safe surgical resection. In addition to open skull-base approaches, the endoscopic endonasal approach to clival chordomas has been reported with favorable albeit early results. Adjuvant radiation is prescribed following complete resection, alternatively for gross residual disease or at the time of recurrence. The modalities of adjuvant radiation therapy reported vary widely and include proton-beam, carbon-ion, fractionated photon radiotherapy, and photon and gamma-knife radiosurgery. As of now, no direct comparison is available, and high-level evidence demonstrating superiority of one modality over another is lacking. While systemic therapies have yet to form part of any first-line therapy for chordomas, a number of targeted agents have been evaluated to date that inhibit specific molecules and their respective pathways known to be implicated in chordomas. These include EGFR (erlotinib, gefitinib, lapatinib), PDGFR (imatinib), mTOR (rapamycin), and VEGF (bevacizumab). This article provides an update of the current multimodality treatment of cranial base chordomas, with an emphasis on how current understanding of molecular pathogenesis provides a framework for the development of novel targeted approaches.

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              Novel cancer immunotherapy agents with survival benefit: recent successes and next steps.

              The US Food and Drug Administration (FDA) recently approved two novel immunotherapy agents, sipuleucel-T and ipilimumab, which showed a survival benefit for patients with metastatic prostate cancer and melanoma, respectively. The mechanisms by which these agents provideclinical benefit are not completely understood. However, knowledge of these mechanisms will be crucial for probing human immune responses and tumour biology in order to understand what distinguishes responders from non-responders. The following next steps are necessary: first, the development of immune-monitoring strategies for the identification of relevant biomarkers; second, the establishment of guidelines for the assessment of clinical end points; and third, the evaluation of combination therapy strategies to improve clinical benefit.
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                Author and article information

                Journal
                Ther Clin Risk Manag
                Ther Clin Risk Manag
                Therapeutics and Clinical Risk Management
                Therapeutics and Clinical Risk Management
                Dove Medical Press
                1176-6336
                1178-203X
                2015
                26 May 2015
                : 11
                : 873-883
                Affiliations
                [1 ]Division of Neurosurgery, Jewish General Hospital, McGill University, Montreal, QC, Canada
                [2 ]Department of Pathology and Laboratory Medicine, Vancouver General Hospital, University of British Columbia, Vancouver, BC, Canada
                [3 ]National Neuroscience Institute, Department of Neurosurgery, King Fahad Medical City, Riyadh, Saudi Arabia
                [4 ]Department of Neurology and Neurosurgery, The Montreal Neurological Institute and Hospital, McGill University Health Centre, Montreal, QC, Canada
                [5 ]Department of Neurological Surgery, University of Washington, University of Washington Medical Center, Seattle, WA, USA
                Author notes
                Correspondence: Salvatore Di Maio, Division of Neurosurgery, Jewish General Hospital, McGill University, 3755 Chemin de la Côte-Sainte-Catherine, Montreal, QC H3T 1E2, Canada, Tel +1 514 340 8222 ext 5200, Fax +1 514 340 7924, Email sdimaio@ 123456jgh.mcgill.ca
                Article
                tcrm-11-873
                10.2147/TCRM.S50526
                4451853
                © 2015 Di Maio et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License

                The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                Categories
                Review

                Medicine

                molecular genetics, chordomas, surgery, skull-base neoplasms, radiation therapy, cell lines

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