H3K27-altered diffuse midline glioma: a paradigm shifting opportunity in direct delivery of targeted therapeutics.
H3K27-altered diffuse midline glioma: a paradigm shifting opportunity in direct delivery of targeted therapeutics.
复制标题
H3K27 改变的弥漫性中线神经胶质瘤：直接提供靶向治疗的范式转变机会。
DOI：
10.1080/14728222.2023.2177531
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发表时间：
2023
影响因子：
5.8
通讯作者：
Daniels,DavidJ
中科院分区：
文献类型：
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作者：
Rechberger,JulianS;Power,BlakeT;Power,EricaA;Nesvick,CodyL;Daniels,DavidJ
Introduction尽管取得了很大的进展，预后为H3 K27-改变弥漫性中线胶质瘤（DMG），以前被称为弥漫性内在脑桥胶质瘤时，位于brainstem.Areas coveredA丰富的研究在过去的十年中已经彻底改变了我们的理解DMG的分子基础，揭示了潜在的靶向治疗这种致命的儿童癌症的脆弱性，仍然黑暗和惨淡。然而，新疗法的成功临床实施仍然存在障碍，包括有效地穿过血脑屏障（BBB）递送到肿瘤部位。在这里，我们回顾了相关文献和临床试验，并讨论了通过对流增强输送（CED）直接给药作为DMG的一种有前途的治疗方式。我们概述了一个全面的分子，药理学和程序的方法，可能会提供希望的患者和他们的family.Expert opinionChallenges仍然在成功的药物输送到DMG。虽然CED和其他技术提供了绕过BBB的机会，但影响成功肿瘤内靶向的变量众多且复杂。我们讨论这些变量和潜在的解决方案，可能导致成功的临床前有前途的治疗药物的临床实施。
IntroductionDespite much progress, the prognosis for H3K27-altered diffuse midline glioma (DMG), previously known as diffuse intrinsic pontine glioma when located in the brainstem, remains dark and dismal.Areas coveredA wealth of research over the past decade has revolutionized our understanding of the molecular basis of DMG, revealing potential targetable vulnerabilities for treatment of this lethal childhood cancer. However, obstacles to successful clinical implementation of novel therapies remain, including effective delivery across the blood–brain barrier (BBB) to the tumor site. Here, we review relevant literature and clinical trials and discuss direct drug delivery via convection-enhanced delivery (CED) as a promising treatment modality for DMG. We outline a comprehensive molecular, pharmacological, and procedural approach that may offer hope for afflicted patients and their families.Expert opinionChallenges remain in successful drug delivery to DMG. While CED and other techniques offer a chance to bypass the BBB, the variables influencing successful intratumoral targeting are numerous and complex. We discuss these variables and potential solutions that could lead to the successful clinical implementation of preclinically promising therapeutic agents.