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首页> 外文期刊>Neurosurgical focus >Potential evolution of neurosurgical treatment paradigms for craniopharyngioma based on genomic and transcriptomic characteristics
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Potential evolution of neurosurgical treatment paradigms for craniopharyngioma based on genomic and transcriptomic characteristics

机译：基于基因组和转录组特征的颅咽管瘤神经外科治疗范式的潜在演变

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The recent genomic and transcriptomic characterization of human craniopharyngiomas has provided important insights into the pathogenesis of these tumors and supports that these tumor types are distinct entities. Critically, the insights provided by these data offer the potential for the introduction of novel therapies and surgical treatment paradigms for these tumors, which are associated with high morbidity rates and morbid conditions. Mutations in the CTNNB1 gene are primary drivers of adamantinomatous craniopharyngioma (ACP) and lead to the accumulation of beta-catenin protein in a subset of the nuclei within the neoplastic epithelium of these tumors. Dysregulation of epidermal growth factor receptor (EGFR) and of sonic hedgehog (SHH) signaling in ACP suggest that paracrine oncogenic mechanisms may underlie ACP growth and implicate these signaling pathways as potential targets for therapeutic intervention using directed therapies. Recent work shows that ACP cells have primary cilia, further supporting the potential importance of SHH signaling in the pathogenesis of these tumors. While further preclinical data are needed, directed therapies could defer, or replace, the need for radiation therapy and/or allow for less aggressive surgical interventions. Furthermore, the prospect for reliable control of cystic disease without the need for surgery now exists. Studies of papillary craniopharyngioma (PCP) are more clinically advanced than those for ACP. The vast majority of PCPs harbor the BRAF(v600e) mutation. There are now 2 reports of patients with PCP that had dramatic therapeutic responses to targeted agents. Ongoing clinical and research studies promise to not only advance our understanding of these challenging tumors but to offer new approaches for patient management.
机译：最近人类颅咽癌的最新基因组和转录组织表征已经为这些肿瘤的发病机制提供了重要的见解，并支持这些肿瘤类型是不同的实体。批判性地，这些数据提供的见解提供了引入新疗法和这些肿瘤的外科治疗范例的可能性，这与高发病率和病态条件相关。 CTNNB1基因中的突变是氨坦蒽曲癣菌瘤（ACP）的初级驱动器，并导致β-连环蛋白蛋白在这些肿瘤的肿瘤上皮内的核的子集中积累。表皮生长因子受体（EGFR）和Sonic Hedgehog（SHH）信号传导的表皮生长因子受体（EGFR）表明，邻静脉致癌机制可能提高ACP生长，并将这些信号传导途径视为使用定向疗法治疗干预的潜在目标。最近的工作表明，ACP细胞具有原发性纤毛，进一步支持SHH信号在这些肿瘤发病机制中的潜在重要性。虽然需要进一步的临床前数据，但导向疗法可以推迟或更换，需要对放射治疗和/或允许更侵略性的外科手术干预措施。此外，现在存在无需手术的囊性疾病可靠控制的前景。乳头状颅咽管瘤（PCP）的研究比ACP的临床前进。绝大多数PCP涉及BRAF（V600E）突变。现在有2例PCP患者对靶向剂的急性反应急剧反应。正在进行的临床和研究申请不仅承诺推进我们对这些挑战性肿瘤的理解，而是为患者管理提供新方法。

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