1Pediatric Neurosurgery, Children's Hospital Colorado, University of Colorado School of Medicine; and.
2Morgan Adams Foundation Pediatric Brain Tumor Program, Aurora, Colorado.
Neurosurg Focus. 2020 Jan 1;48(1):E7. doi: 10.3171/2019.10.FOCUS19705.
The evolving characterization of the biological basis of adamantinomatous craniopharyngioma (ACP) has provided insights critical for novel systemically delivered therapies. While current treatment strategies for ACP are associated with low mortality rates, patients experience severely lowered quality of life due to high recurrence rates and chronic sequelae, presenting a need for novel effective treatment regimens. The identification of various dysregulated pathways that play roles in the pathogenesis of ACP has prompted the investigation of novel treatment options. Aberrations in the CTNNB1 gene lead to the dysregulation of the Wnt pathway and the accumulation of nuclear β-catenin, which may play a role in tumor invasiveness. While Wnt pathway/β-catenin inhibition may be a promising treatment for ACP, potential off-target effects have limited its use in current intervention strategies. Promising evidence of the therapeutic potential of cystic proinflammatory mediators and immunosuppressants has been translated into clinical therapies, including interleukin 6 and IDO-1 inhibition. The dysregulation of the pathways of mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK), epidermal growth factor receptor (EGFR), and programmed cell death protein 1 and its ligand (PD-1/PD-L1) has led to identification of various therapeutic targets that have shown promise as clinical strategies. The Sonic Hedgehog (SHH) pathway is upregulated in ACP and has been implicated in tumorigenesis and tumor growth; however, inhibition of SHH in murine models decreased survival, limiting its therapeutic application. While further preclinical and clinical data are needed, systemically delivered therapies could delay or replace the need for more aggressive definitive treatments. Ongoing preclinical investigations and clinical trials of these prospective pathways promise to advance treatment approaches aimed to increase patients' quality of life.
颅咽管瘤（ACP）生物学基础的不断深入研究为新型系统治疗方法提供了重要的见解。尽管目前治疗 ACP 的策略死亡率较低，但由于高复发率和慢性后遗症，患者的生活质量严重下降，因此需要新的有效治疗方案。各种失调途径的鉴定在 ACP 的发病机制中起作用，促使人们研究新的治疗选择。CTNNB1 基因突变导致 Wnt 途径失调和核β-catenin 积累，这可能在肿瘤侵袭性中起作用。虽然 Wnt 途径/β-catenin 抑制可能是 ACP 的一种有前途的治疗方法，但潜在的脱靶效应限制了其在当前干预策略中的应用。囊性促炎介质和免疫抑制剂的治疗潜力的有希望证据已转化为临床治疗，包括白细胞介素 6 和 IDO-1 抑制。丝裂原激活的蛋白激酶/细胞外信号调节激酶（MAPK/ERK）、表皮生长因子受体（EGFR）和程序性细胞死亡蛋白 1 及其配体（PD-1/PD-L1）途径的失调导致各种治疗靶点的鉴定，这些靶点已显示出作为临床策略的潜力。Sonic Hedgehog（SHH）途径在 ACP 中上调，并与肿瘤发生和肿瘤生长有关；然而，在小鼠模型中抑制 SHH 会降低生存率，限制了其治疗应用。虽然需要进一步的临床前和临床数据，但系统递送的治疗方法可以延迟或替代更积极的确定性治疗的需求。这些潜在途径的正在进行的临床前研究和临床试验有望推进旨在提高患者生活质量的治疗方法。
