{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:25:43Z","timestamp":1790778343439,"version":"4.1.0"},"reference-count":111,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,3,4]],"date-time":"2021-03-04T00:00:00Z","timestamp":1614816000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Chordoma is a low-grade notochordal tumor of the skull base, mobile spine and sacrum which behaves malignantly and confers a poor prognosis despite indolent growth patterns. These tumors often present late in the disease course, tend to encapsulate adjacent neurovascular anatomy, seed resection cavities, recur locally and respond poorly to radiotherapy and conventional chemotherapy, all of which make chordomas challenging to treat. Extent of surgical resection and adequacy of surgical margins are the most important prognostic factors and thus patients with chordoma should be cared for by a highly experienced, multi-disciplinary surgical team in a quaternary center. Ongoing research into the molecular pathophysiology of chordoma has led to the discovery of several pathways that may serve as potential targets for molecular therapy, including a multitude of receptor tyrosine kinases (e.g., platelet-derived growth factor receptor [PDGFR], epidermal growth factor receptor [EGFR]), downstream cascades (e.g., phosphoinositide 3-kinase [PI3K]\/protein kinase B [Akt]\/mechanistic target of rapamycin [mTOR]), brachyury\u2014a transcription factor expressed ubiquitously in chordoma but not in other tissues\u2014and the fibroblast growth factor [FGF]\/mitogen-activated protein kinase kinase [MEK]\/extracellular signal-regulated kinase [ERK] pathway. In this review article, the pathophysiology, diagnosis and modern treatment paradigms of chordoma will be discussed with an emphasis on the ongoing research and advances in the field that may lead to improved outcomes for patients with this challenging disease.<\/jats:p>","DOI":"10.3390\/jcm10051054","type":"journal-article","created":{"date-parts":[[2021,3,4]],"date-time":"2021-03-04T21:58:07Z","timestamp":1614895087000},"page":"1054","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":114,"title":["Chordoma\u2014Current Understanding and Modern Treatment Paradigms"],"prefix":"10.3390","volume":"10","author":[{"given":"Sean M.","family":"Barber","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Houston Methodist Neurological Institute, Houston Methodist Hospital, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saeed S.","family":"Sadrameli","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Houston Methodist Neurological Institute, Houston Methodist Hospital, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan J.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Houston Methodist Neurological Institute, Houston Methodist Hospital, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jared S.","family":"Fridley","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Rhode Island Hospital, The Warren Alpert Medical School at Brown University, Providence, RI 02903, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin S.","family":"Teh","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Houston Methodist Neurological Institute, Houston Methodist Hospital, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adetokunbo A.","family":"Oyelese","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Rhode Island Hospital, The Warren Alpert Medical School at Brown University, Providence, RI 02903, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert E.","family":"Telfeian","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Rhode Island Hospital, The Warren Alpert Medical School at Brown University, Providence, RI 02903, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziya L.","family":"Gokaslan","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Rhode Island Hospital, The Warren Alpert Medical School at Brown University, Providence, RI 02903, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,4]]},"reference":[{"key":"ref_1","unstructured":"Virchow, R. 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