Department of Neurologic Surgery, Mayo Clinic, Rochester, MN, USA.
Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic Graduate School of Biomedical Sciences, Rochester, MN, USA.
Expert Opin Ther Targets. 2023 Jan;27(1):9-17. doi: 10.1080/14728222.2023.2177531. Epub 2023 Feb 12.
Despite 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.
A 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.
Challenges 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.
尽管已经取得了很大的进展，但 H3K27 改变的弥漫性中线胶质瘤（DMG）的预后仍然很黯淡，当位于脑干时，这种肿瘤以前被称为弥漫性内在脑桥胶质瘤。
在过去十年中，大量的研究彻底改变了我们对 DMG 分子基础的理解，揭示了针对这种致命儿童癌症的潜在治疗靶点。然而，新型治疗方法成功临床应用的障碍仍然存在，包括有效地将药物递送到血脑屏障（BBB）以外的肿瘤部位。在这里，我们回顾了相关的文献和临床试验，并讨论了通过对流增强输送（CED）进行直接药物输送作为治疗 DMG 的一种有前途的治疗方式。我们概述了一种全面的分子、药理学和程序方法，为患病患者及其家属带来了希望。
成功将药物递送到 DMG 仍然存在挑战。虽然 CED 和其他技术提供了绕过 BBB 的机会，但影响肿瘤内靶向成功的变量很多且复杂。我们讨论了这些变量和潜在的解决方案，这些方案可能会导致有前途的治疗剂在临床前阶段的成功实施。
