Somaiah Neeta, Tap William
Department of Sarcoma Medical Oncology, Division of Cancer Medicine, MD Anderson Cancer Center, Houston, TX, United States.
Sarcoma Medical Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, United States.
Cancer Treat Rev. 2024 Jan;122:102668. doi: 10.1016/j.ctrv.2023.102668. Epub 2023 Dec 10.
Well-differentiated and dedifferentiated liposarcomas (WDLPS and DDLPS) are rare tumors that arise from lipocytes in soft tissue. There is a high unmet need in patients with these liposarcomas given poor outcomes, particularly for DDLPS. WDLPS and DDLPS share important genetic and histological characteristics - most notably, the amplification of the 2 genes MDM2 and CDK4. Both genes are considered oncogenes because of their ability to shut down tumor suppressor pathways. There are multiple therapeutic approaches that aim to target MDM2 and CDK4 activity for the purpose of restoring intrinsic tumor suppressor cellular response and terminating oncogenesis. However, current understanding of the molecular mechanisms involved in WDLPS and DDLPS pathology is limited. In recent years, significant efforts have been made to refine and implement targeted therapy for this patient population. The use of patient-derived cell and tumor xenograft models has been an important tool for recapitulating WDLPS and DDLPS biology. These models also offer valuable insights for drug development and drug combination studies. Here we offer a review of the current understanding of WDLPS and DDLPS biology and its therapeutic implications.
高分化和去分化脂肪肉瘤（WDLPS和DDLPS）是起源于软组织中脂肪细胞的罕见肿瘤。鉴于这些脂肪肉瘤患者的预后较差，尤其是DDLPS患者，存在着尚未满足的高度需求。WDLPS和DDLPS具有重要的遗传和组织学特征，最显著的是2个基因MDM2和CDK4的扩增。由于这两个基因能够关闭肿瘤抑制途径，它们都被视为癌基因。有多种治疗方法旨在靶向MDM2和CDK4的活性，以恢复内在的肿瘤抑制细胞反应并终止肿瘤发生。然而，目前对WDLPS和DDLPS病理所涉及的分子机制的了解有限。近年来，已经做出了重大努力来完善和实施针对这一患者群体的靶向治疗。使用患者来源的细胞和肿瘤异种移植模型一直是重现WDLPS和DDLPS生物学特性的重要工具。这些模型也为药物开发和药物联合研究提供了有价值的见解。在此，我们对目前对WDLPS和DDLPS生物学的理解及其治疗意义进行综述。
