Clinical and molecular approaches to well differentiated and dedifferentiated liposarcoma.
Clinical and molecular approaches to well differentiated and dedifferentiated liposarcoma.
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DOI：
10.1097/cco.0b013e32834796e6
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发表时间：
2011-07
影响因子：
3.4
通讯作者：
Singer S
中科院分区：
文献类型：
--
作者：
Crago AM;Singer S
脂肪肉瘤是一种罕见的疾病，可分为五种组织学亚型。这些包括分化良好的脂肪肉瘤（WDLS）和去分化脂肪肉瘤（DDLS），其特征均为染色体12 q13 -15扩增。本综述将集中于WDLS和DDLS的临床管理，并检查最近的分子研究，有可能影响临床管理。WDLS和DDLS患者的结局取决于手术切除的完整性以及肿瘤位置和组织学亚型。去分化组织学或腹膜后位置的患者复发风险较高。我们现在了解到，对于快速生长或不能完全切除的肿瘤患者，手术结果很差，因此这些患者应采用非手术治疗。放疗和化疗在WDLS和DDLS中的反应率较低，但靶向12号染色体基因产物MDM 2和CDK 4的新型药物在临床前研究中显示出前景，并正在临床试验中进行测试。细胞系、组织微阵列和基因组分析已经确定了其他靶点，包括ZIC 1、TOP 2A、AURKA和IGF-1 R，这些靶点可能成为未来治疗的基础。尽管完全手术切除是目前WDLS和DDLS最有效的治疗方法，但大多数腹膜后脂肪肉瘤患者最终会复发并死于疾病。人们希望，一个多模态的方法，其中包括靶向治疗和完整的手术切除，将显着改善患者的结果。
Liposarcoma, a rare disease, is classified into five histologic subtypes. These include well-differentiated liposarcoma (WDLS) and dedifferentiated liposarcoma (DDLS), both characterized by chromosome 12q13-15 amplification. This review will focus on the clinical management of WDLS and DDLS and examine recent molecular studies that have the potential to affect clinical management. Outcome of patients with WDLS and DDLS depends on completeness of surgical resection as well as tumor location and histologic subtype. Risk of recurrence is high for patients with dedifferentiated histology or retroperitoneal location. We now understand that surgical outcomes are poor for patients with rapidly growing or incompletely resectable tumors, so these patients should be managed non-operatively. Radiation and chemotherapy have low response rates in WDLS and DDLS, but novel agents targeted at chromosome 12 gene products MDM2 and CDK4 have shown promise in pre-clinical studies and are being tested in clinical trials. Cell line, tissue microarray, and genomic analyses have identified additional targets including ZIC1, TOP2A, AURKA, and IGF-1R, which could form the basis of future therapies. Although complete surgical resection is currently the most effective treatment for WDLS and DDLS, the majority of patients with retroperitoneal liposarcoma will eventually have recurrence and die of disease. It is hoped that a multi-modality approach, which incorporates targeted therapies and complete surgical resection, will significantly improve patient outcomes.