← 返回前沿论文

H3K27M 突变型弥漫性内生性脑桥胶质瘤管理的最新进展:一项叙述性综述

英文原题:Latest Advancements in the Management of H3K27M-Mutant Diffuse Intrinsic Pontine Glioma: A Narrative Review.

PubMed 2025/01/27(内容时间) Cancers (Basel) Q2 · IF 4.8(JCR 2025)

研究概要

尽管近年来在弥漫性内生性桥脑胶质瘤(DIPG)的放疗方面取得了进展,但该病的预后仍然很差,凸显出需要新的治疗策略来改善结局。

中文摘要

尽管近年来在弥漫性内生性桥脑胶质瘤(DIPG)的放疗方面取得了进展,但该病的预后仍然很差,这凸显了需要新的治疗策略来改善预后。在DIPG患儿的诊断过程中加入立体定向活检对于改善该疾病的管理至关重要。事实上,H3K27M突变作为DIPG关键驱动因素的发现,促进了比传统药物更有效的新药的开发。这些药物包括尼妥珠单抗(一种抗EGFR药物)和长春瑞滨(一种半合成长春花生物碱)的联合方案、帕比司他(一种组蛋白去乙酰化酶抑制剂)、ONC201(一种阻断多巴胺受体D2并使Akt和ERK激酶失活的药物)以及嵌合抗原受体(CAR)T细胞。在局部治疗方面,识别H3K27M突变可以帮助我们探索遗传改变如何影响治疗反应、复发模式和生存。除了首次复发时间之外,特定的肿瘤复发模式,如软脑膜播散,也会影响治疗计划。例如,可以根据肿瘤的侵袭性调整放疗的剂量和体积。由于H3K27M突变与更高的恶性程度相关,第二轮局部照射可以使用稍高的剂量。此外,照射整个颅脊轴可以帮助控制局部和软脑膜疾病。

展开英文摘要原文

Despite recent advancements in radiotherapy for Diffuse Intrinsic Pontine Glioma (DIPG), the prognosis of this disease remains poor, highlighting the need for new treatment strategies to improve outcomes. Adding stereotactic biopsy to the diagnostic process for children with DIPG has been crucial in improving the management of this disease. Indeed, the discovery of the H3K27M mutation as a key driver of DIPG has led to the development of new drugs that are more effective than traditional ones. These include nimotuzumab (an anti-EGFR drug) and vinorelbine (a semisynthetic vinca alkaloid) in combination, Panobinostat (a histone deacetylase inhibitor), ONC201 (a drug that blocks the dopamine receptor D2 and inactivates Akt and ERK kinases), and chimeric antigen receptor (CAR) T cells. In terms of local therapy, identifying the H3K27M mutation can help us explore how genetic changes affect treatment response, recurrence patterns, and survival. Beyond the time to first recurrence, specific patterns of tumor recurrence, like leptomeningeal spread, can influence treatment plans. For example, radiotherapy can be adjusted in terms of doses and volumes, based on tumor aggressiveness. Because the H3K27M mutation is linked to higher malignancy, a slightly higher dose could be used for the second round of local irradiation. Additionally, irradiating the entire craniospinal axis could help control both local and leptomeningeal disease.

论文信息

作者
Lo Greco MC、Marano G、La Rocca M、Acquaviva G、Milazzotto R、Liardo RLE、Basile A、Foti PV
第一作者单位
Radiation Oncology Unit, Department of Biomedical, Dental and Morphological and Functional Imaging Sciences, University of Messina, 98122 Messina, Italy.Italy
通讯作者单位
Radiation Oncology Unit, University Hospital Policlinico "G. Rodolico-San Marco", 95123 Catania, Italy.Italy
文献类型
综述
期刊
Cancers2025 Jan 27
原文标识
PubMed 39941789 · DOI 10.3390/cancers17030420