Liposarcoma (LPS) is one of the most common adult soft-tissue sarcomas (STS), characterized by a high diversity of histopathological features as well as to a lesser extent by a spectrum of molecular abnormalities. Current targeted therapies for STS do not include a wide range of drugs and surgical resection is the mainstay of treatment for localized disease in all subtypes, while many LPS patients initially present with or ultimately progress to advanced disease that is either unresectable, metastatic or both. The understanding of the molecular characteristics of liposarcoma subtypes is becoming an important option for the detection of new potential targets and development novel, biology-driven therapies for this disease. Innovative therapies have been introduced and they are currently part of preclinical and clinical studies. In this review, we provide an analysis of the molecular genetics of liposarcoma followed by a discussion of the specific epigenetic changes in these malignancies. Then, we summarize the peculiarities of the key signaling cascades involved in the pathogenesis of the disease and possible novel therapeutic approaches based on a better understanding of subtype-specific disease biology. Although heterogeneity in liposarcoma genetics and phenotype as well as the associated development of resistance to therapy make difficult the introduction of novel therapeutic targets into the clinic, recently a number of targeted therapy drugs were proposed for LPS treatment. The most promising results were shown forCDK4/6 andMDM2inhibitors as well as for the multi-kinase inhibitors anlotinib and sunitinib.
脂肪肉瘤（LPS）是最常见的成人软组织肉瘤（STS）之一，其特点在于组织病理学特征具有高度多样性，并在一定程度上伴有一系列分子异常。目前针对STS的靶向治疗药物种类有限，手术切除是所有亚型局限性病变的主要治疗手段，而许多脂肪肉瘤患者在初诊时即表现为或最终进展为无法切除、转移性或两者兼有的晚期疾病。理解脂肪肉瘤亚型的分子特征，正成为发现新潜在靶点及开发基于疾病生物学的新型疗法的重要方向。创新疗法已被提出，目前正处于临床前及临床研究阶段。本综述首先分析了脂肪肉瘤的分子遗传学特征，进而探讨了这类恶性肿瘤的特异性表观遗传学改变。随后，我们总结了参与疾病发病机制的关键信号通路的特性，以及基于对亚型特异性疾病生物学的深入理解可能产生的新型治疗策略。尽管脂肪肉瘤在遗传学、表型方面的异质性以及由此产生的治疗耐药性使得新型治疗靶点的临床转化面临挑战，但近期已有多种靶向治疗药物被提出用于脂肪肉瘤治疗。其中CDK4/6抑制剂、MDM2抑制剂以及多激酶抑制剂安罗替尼和舒尼替尼已显示出最具前景的治疗效果。
Genetic, Epigenetic and Transcriptome Alterations in Liposarcoma for Target Therapy Selection
肿瘤(癌症)患者之家