Lo Greco Maria Chiara, Marano Giorgia, La Rocca Madalina, Acquaviva Grazia, Milazzotto Roberto, Liardo Rocco Luca Emanuele, Basile Antonio, Foti Pietro Valerio, Palmucci Stefano, David Emanuele, Parisi Silvana, Pontoriero Antonio, Pergolizzi Stefano, Spatola Corrado
Radiation Oncology Unit, Department of Biomedical, Dental and Morphological and Functional Imaging Sciences, University of Messina, 98122 Messina, Italy.
Radiation Oncology Unit, University Hospital Policlinico "G. Rodolico-San Marco", 95123 Catania, Italy.
Cancers (Basel). 2025 Jan 27;17(3):420. doi: 10.3390/cancers17030420.
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.
尽管近年来弥漫性脑桥内在胶质瘤（DIPG）的放射治疗取得了进展，但该疾病的预后仍然很差，这凸显了需要新的治疗策略来改善治疗结果。在DIPG患儿的诊断过程中增加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的关键驱动因素的发现，促使了比传统药物更有效的新药的研发。这些药物包括联合使用的尼妥珠单抗（一种抗表皮生长因子受体药物）和长春瑞滨（一种半合成长春花生物碱）、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突变有助于我们探索基因变化如何影响治疗反应、复发模式和生存。除了首次复发时间外，肿瘤复发的特定模式，如软脑膜播散，会影响治疗计划。例如，可根据肿瘤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，第二轮局部照射可使用略高的剂量。此外，对整个颅脊髓轴进行照射有助于控制局部和软脑膜疾病。
