尽管放射治疗和手术治疗取得了鼓舞人心的进展，脊索瘤依然对化疗具有抗药性，而且局部复发很常见。尽管复发的主要机制是局部性的，但在少数患者中也会出现转移性疾病。如果不小心完全切除开放活检径路，复发也可能沿手术切口发生。在疾病复发时，重新手术的发病率增加，放射治疗可作为初发疾病的细胞减量或复发疾病的选择，虽然高剂量治疗可能会出现毒性反应。鉴于这些挑战，需要有针对性的术后辅助治疗化疗药物。 在本综述中，我们总结了脊索瘤的遗传驱动因子以及当前脊索瘤免疫治疗和表观遗传学研究的现状。脊索瘤是一种异质性肿瘤，应该从不同角度进行靶向治疗，对其特征的研究，从分子学到免疫学再到表观遗传学，是必要的。结合不侵入性患者甲基化模式的研究、基于组织的分子和药物筛选，可以通过不同来源的预后机制指导治疗决策，同时有助于个体化的手术计划和治疗，从而转变患者护理。

Despite encouraging advances in radiation and surgical treatment, chordomas remain resistant to chemotherapy and local recurrence is common. Although the primary mechanism of recurrence is local, metastatic disease occurs in a small subset of patients. Recurrence may also occur along the surgical trajectory if care is not taken to fully excise the open biopsy pathway. There is increasing morbidity with reoperation upon disease recurrence, and radiation is an option for cytoreduction in primary disease or for recurrent disease, although toxicity may be observed with high-dose therapies. Given these challenges, targeted chemotherapeutic agents for postoperative adjuvant treatment are needed.In this review, we summarize the genetic drivers of chordoma and the state of the current research in chordoma immunotherapy and epigenetics.Chordoma is a heterogenous tumor that should be targeted from different angles and the study of its characteristics, from molecular to immunological to epigenetic, is necessary. Combining different approaches, such as studying noninvasive patient methylation patterns with tissue-based molecular and drug screening, can transform patient care by guiding treatment decisions based on prognostic mechanisms from different sources, while helping individualize surgical planning and treatment.