Qiu Tong, Xiang Shanshan, Zhou Jiangyuan, Yang Min, Lan Yuru, Zhang Xuepeng, Gong Xue, Zhang Zixin, Ji Yi
Division of Oncology, Department of Pediatric Surgery and Med-X Center for Informatics, West China Hospital of Sichuan University, Chengdu, China.
Pediatric Intensive Care Unit, Department of Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, China.
Int J Cancer. 2025 Feb 15;156(4):689-699. doi: 10.1002/ijc.35207. Epub 2024 Oct 6.
Kaposiform hemangioendotheliomas (KHEs) are vascular tumors that are considered borderline or locally aggressive and may lead to lethal outcomes. Traditional therapies, such as surgery and embolization, may be insufficient or technically impossible for patients with KHE. Sirolimus (or rapamycin), a specific inhibitor of mechanistic target of rapamycin, has recently been demonstrated to be very useful in the treatment of KHEs. Here, we highlight recent substantial progress regarding the effects of sirolimus on KHEs and discuss the potential mechanisms of action of sirolimus in treating this disease. The prevention of platelet activation and inflammation, along with antiangiogenic effects, the inhibition of lymphangiogenesis, the attenuation of fibrosis, or a combination of all these effects, may be responsible for the therapeutic effects of sirolimus. In addition, the mechanism of sirolimus resistance in some KHE patients is discussed. Finally, we review the somatic mutations that have recently been identified in KEH lesions, and discuss the potential of novel therapeutic targets based on these further understandings of the cellular and molecular pathogenesis of KHE.
卡波西样血管内皮瘤（KHEs）是一种血管肿瘤，被认为具有交界性或局部侵袭性，可能导致致命后果。传统治疗方法，如手术和栓塞，对于KHE患者可能并不充分或在技术上无法实施。西罗莫司（或雷帕霉素）是雷帕霉素作用机制的特异性抑制剂，最近已被证明在治疗KHEs方面非常有效。在此，我们重点介绍西罗莫司对KHEs作用的近期重大进展，并讨论西罗莫司治疗该疾病的潜在作用机制。预防血小板活化和炎症，以及抗血管生成作用、抑制淋巴管生成、减轻纤维化，或所有这些作用的组合，可能是西罗莫司治疗效果的原因。此外，还讨论了一些KHE患者中对西罗莫司耐药的机制。最后，我们回顾了最近在KEH病变中鉴定出的体细胞突变，并基于对KHE细胞和分子发病机制的这些进一步理解，讨论了新型治疗靶点的潜力。
