文章：

恶性颗粒细胞瘤中的抗血管生成疗法：文献综述

Antiangiogenics in Malignant Granular Cell Tumors: Review of the Literature

原文发布日期：28 October 2023

DOI: 10.3390/cancers15215187

类型: Article

开放获取: 是

英文摘要：

Granular cell tumors (GCT) represent 0.5% of all soft tissue sarcomas (STS), and when metastatic, they exhibit aggressive behavior and determine limited survival. Metastatic GCTs are relatively chemo-resistant; however, there is growing evidence of the benefit of using pazopanib and other targeted therapies in this histology. This is a review of the role of pazopanib and other targeted therapies in the treatment of GCTs, along with some insights on pathology and molecular biology described in GCTs. From 256 articles found in our search, 10 case-report articles met the inclusion criteria. Pazopanib was the most employed systemic therapy. The median reported time on therapy with pazopanib was seven months. Eight out of ten patients (80%) experienced disease control with pazopanib, while four out of ten (40%) patients achieved an objective RECIST response. Molecular studies suggested that antitumoral effects of pazopanib in GCT might be due to a loss-of-function ofATP6AP1/2genes which consequently enhance signaling through several molecular pathways, such as SFKs, STAT5a/b, and PDGFR-β. Other reported targeted therapies for malignant GCTs included pazopanib in combination with crizotinib, which showed disease control for four months in one patient, and a PI3K inhibitor which achieved disease control for nine months in another patient. Dasatinib and megestrol were ineffective in two other different patients. Pazopanib has been demonstrated to be active in advanced GCTs and may be considered as a preferable treatment option.

摘要翻译： 

颗粒细胞瘤占所有软组织肉瘤的0.5%，发生转移时具有侵袭性行为且患者生存期有限。转移性颗粒细胞瘤对化疗相对耐药，但越来越多的证据表明帕唑帕尼及其他靶向治疗对该组织学类型有效。本文综述了帕唑帕尼及其他靶向疗法在颗粒细胞瘤治疗中的作用，并对该肿瘤的病理学和分子生物学特征进行了探讨。通过文献检索获得256篇相关文章，其中10篇病例报告符合纳入标准。帕唑帕尼是最常用的全身治疗方案，中位治疗时间为七个月。10例患者中有8例（80%）通过帕唑帕尼治疗实现疾病控制，其中4例（40%）达到客观RECIST标准缓解。分子研究表明，帕唑帕尼在颗粒细胞瘤中的抗肿瘤作用可能与ATP6AP1/2基因功能缺失有关，该缺失通过增强SFKs、STAT5a/b和PDGFR-β等多条分子通路信号传导发挥作用。其他针对恶性颗粒细胞瘤的靶向治疗包括帕唑帕尼联合克唑替尼方案（使1例患者实现四个月疾病控制）及PI3K抑制剂单药治疗（使另1例患者实现九个月疾病控制）。达沙替尼和甲地孕酮在另外两例不同患者中未见疗效。现有证据表明帕唑帕尼对晚期颗粒细胞瘤具有治疗活性，可被视为优选治疗方案。

原文链接：

Antiangiogenics in Malignant Granular Cell Tumors: Review of the Literature