Department of Neurological Surgery, University of California at San Francisco, San Francisco, California 94117, USA.
Neurosurgery. 2011 Jan;68(1):231-40; discussion 240-1. doi: 10.1227/NEU.0b013e3181fd2ac5.
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.
To highlight potential clinical trials that could evolve from new insights into the molecular biology of chordoma.
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.
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.
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.
脊索瘤是一种罕见的局部侵袭性恶性肿瘤，常表现出隐匿的自然病史，难以根除。手术和放疗是脊索瘤的主要治疗方法，但局部复发的机会仍然很高。复发或不能进行完整整块切除的患者预后通常较差。需要新的药物用于脊索瘤术后辅助治疗。
强调可能从脊索瘤分子生物学的新见解中发展出来的潜在临床试验。
我们对最近发表的文献中描述脊索瘤分子特征的研究进行了综述，并根据这些知识，确定了几个潜在的临床治疗靶点。
几种受体酪氨酸激酶及其下游信号级联在脊索瘤中表现出失调，是未来治疗干预的有吸引力的靶点。在脊索瘤中特别重要的途径涉及血小板衍生生长因子受体、表皮生长因子受体、肝细胞生长因子受体以及磷酸肌醇 3-激酶、Akt 和雷帕霉素的哺乳动物靶标等常见下游级联。
最近描述脊索瘤分子生物学的发现为未来的临床试验照亮了多个可能的靶点。针对这些异常途径的抑制剂的可用性使脊索瘤和其他癌症的分子治疗临床试验既可行又可立即实现。此外，我们强调了在实施脊索瘤和其他癌症的分子治疗时联合治疗的原理。
