Sarcoma Program, Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94304, USA.
Department of Pathology, Stanford University School of Medicine, Stanford, CA 94304, USA.
Int J Mol Sci. 2023 May 31;24(11):9571. doi: 10.3390/ijms24119571.
Well-differentiated/de-differentiated liposarcoma (WDLPS/DDLPS) is one of the most common histologic subtypes of soft tissue sarcoma (STS); however, treatment options remain limited. WDLPS and DDLPS both exhibit the characteristic amplification of chromosome region 12q13-15, which contains the genes and . DDLPS exhibits higher amplification ratios of these two and carries additional genomic lesions, including the amplification of chromosome region 1p32 and chromosome region 6q23, which may explain the more aggressive biology of DDLPS. WDLPS does not respond to systemic chemotherapy and is primarily managed with local therapy, including multiple resections and debulking procedures whenever clinically feasible. In contrast, DDLPS can respond to chemotherapy drugs and drug combinations, including doxorubicin (or doxorubicin in combination with ifosfamide), gemcitabine (or gemcitabine in combination with docetaxel), trabectedin, eribulin, and pazopanib. However, the response rate is generally low, and the response duration is usually short. This review highlights the clinical trials with developmental therapeutics that have been completed or are ongoing, including CDK4/6 inhibitors, MDM2 inhibitors, and immune checkpoint inhibitors. This review will also discuss the current landscape in assessing biomarkers for identifying tumors sensitive to immune checkpoint inhibitors.
去分化/未分化脂肪肉瘤（WDLPS/DDLPS）是软组织肉瘤（STS）中最常见的组织学亚型之一；然而，治疗选择仍然有限。WDLPS 和 DDLPS 均表现出染色体区域 12q13-15 的特征性扩增，该区域包含基因 和 。DDLPS 对这两个基因的扩增比例更高，并携带额外的基因组病变，包括染色体区域 1p32 和染色体区域 6q23 的扩增，这可能解释了 DDLPS 更具侵袭性的生物学特性。WDLPS 对全身化疗无反应，主要通过局部治疗进行管理，包括在临床可行的情况下进行多次切除术和减瘤手术。相比之下，DDLPS 可以对化疗药物和药物组合（包括阿霉素[或阿霉素联合异环磷酰胺]、吉西他滨[或吉西他滨联合多西紫杉醇]、 trabectedin、eribulin 和 pazopanib）产生反应。然而，反应率通常较低，反应持续时间通常较短。本综述重点介绍了已完成或正在进行的开发治疗药物的临床试验，包括 CDK4/6 抑制剂、MDM2 抑制剂和免疫检查点抑制剂。本综述还将讨论目前评估免疫检查点抑制剂敏感肿瘤的生物标志物的情况。
