Abstract：
Chordomas are tumors thought to originate from notochordal remnants that occur in midline structures from the cloves of the skull base to the sacrum. In adults, the most common location is the sacrum, followed by the clivus and then mobile spine, while in children a clival origin is most common. Most chordomas are slow growing. Clinical presentation of chordomas tend to occur late, with local invasion and large size often complicating surgical intervention. Radiation therapy with protons has been proven to be an effective adjuvant therapy. Unfortunately, few adjuvant systemic treatments have demonstrated significant effectiveness, and chordomas tend to recur despite intensive multimodal care. However, insight into the molecular underpinnings of chordomas may guide novel therapeutic approaches including selection for immune and molecular therapies, individualized prognostication of outcomes, and real-time noninvasive assessment of disease burden and evolution. At the genomic level, elevated levels of brachyury stemming from duplications and mutations resulting in altered transcriptional regulation may introduce druggable targets for new surgical adjuncts. Transcriptome and epigenome profiling have revealed promoter- and enhancer-dependent mechanisms of protein regulation, which may influence therapeutic response and long-term disease history. Continued scientific and clinical advancements may offer further opportunities for treatment of chordomas. Single-cell transcriptome profiling has further provided insight into the heterogeneous molecular pathways contributing to chordoma propagation. New technologies such as spatial transcriptomics and emerging biochemical analytes such as cell-free DNA have further augmented the surgeon-clinician\'s armamentarium by facilitating detailed characterization of intra- and intertumoral biology while also demonstrating promise for point-of-care tumor quantitation and assessment. Recent and ongoing clinical trials highlight accelerating interest to translate laboratory breakthroughs in chordoma biology and immunology into clinical care. In this review, the authors dissect the landmark studies exploring the molecular pathogenesis of chordoma. Incorporating this into an outline of ongoing clinical trials and discussion of emerging technologies, the authors aimed to summarize recent advancements in understanding chordoma pathogenesis and how neurosurgical care of chordomas may be augmented by improvements in adjunctive treatments.
摘要：
脊索瘤是被认为起源于从颅底丁香到骶骨的中线结构中出现的脊索残余物的肿瘤。在成年人中,最常见的位置是骶骨，接着是悬崖，然后是移动脊柱，而在儿童中，斜坡起源是最常见的。大多数脊索瘤生长缓慢。脊索瘤的临床表现往往发生较晚，局部侵入和大尺寸经常使手术复杂化。质子放射治疗已被证明是一种有效的辅助治疗。不幸的是,很少有辅助系统治疗显示出显著的有效性，尽管加强了多模式治疗，脊索瘤仍倾向于复发。然而,深入了解脊索瘤的分子基础可能会指导新的治疗方法，包括选择免疫和分子疗法，结果的个性化预测，以及疾病负担和演变的实时非侵入性评估。在基因组层面,由于重复和突变导致转录调节改变而引起的短尾畸形水平升高可能为新的外科辅助药物引入可药用靶标.转录组和表观基因组分析揭示了启动子和增强子依赖的蛋白质调节机制，这可能会影响治疗反应和长期病史。持续的科学和临床进步可能为脊索瘤的治疗提供进一步的机会。单细胞转录组分析进一步提供了对促进脊索瘤传播的异质分子途径的见解。新技术，如空间转录组学和新兴的生化分析物，如无细胞DNA，通过促进肿瘤内和肿瘤间生物学的详细表征，进一步增强了外科医生-临床医生的医疗设备，同时也证明了对护理点肿瘤定量和评估的希望。最近和正在进行的临床试验强调加速将脊索瘤生物学和免疫学的实验室突破转化为临床护理的兴趣。在这次审查中,作者剖析了探索脊索瘤分子发病机制的具有里程碑意义的研究。将其纳入正在进行的临床试验和对新兴技术的讨论的概述中，作者旨在总结在理解脊索瘤发病机制方面的最新进展，以及如何通过改善辅助治疗来增强脊索瘤的神经外科护理。
