Malignant peripheral nerve sheath tumors (MPNSTs) are one of the most difficult sarcomas to treat. Due to the rarity of MPNSTs, many of the therapeutic approaches used are from treatment guidelines for soft tissue sarcoma. Besides surgery, little success has been achieved using these therapies. Traditional chemotherapy and radiation therapy regimens designed to treat sarcoma have unclear efficacy when used to treat MPNSTs. Targeted therapeutics that succeeded in other sarcomas failed to produce positive results in MPNSTs. Moreover, investigational agents that have shown efficacy in preclinical models have produced disappointing outcomes in clinical trials. While therapeutic options for patients with MPNST have remained relatively stagnant, dramatic improvements in therapeutic outcomes of other rare sarcomas have been made. This difference in success is likely caused by the complex heterogeneity of MPNSTs that hinders drug development, although many MPNSTs are associated with neurofibromatosis type 1 (NF1), a genetic disorder resulting from mutations in the NF1 gene that encodes the negative RAS regulator neurofibromin. The development of new agents for MPNST treatment has shifted away from solely targeting RAS pathway gene products to stimulating the immune system and manipulating other MPNST driver mutations such asCDKN2A/B,SUZ12,EED, andTP53. This review presents recent advances in the treatment of sarcomas and the future of drug development targeting MPNSTs.
恶性外周神经鞘瘤（MPNSTs）是最难治疗的肉瘤类型之一。由于其罕见性，目前多数治疗方案参考软组织肉瘤的治疗指南。除手术外，这些疗法取得的成功有限。传统针对肉瘤设计的化疗和放疗方案对MPNSTs的疗效尚不明确，在其他肉瘤中取得成功的靶向治疗在MPNSTs中也未能产生积极效果。此外，临床前模型显示有效的研究性药物在临床试验中的结果令人失望。与其他罕见肉瘤治疗效果的显著提升相比，MPNSTs的治疗选择长期处于相对停滞状态。这种差异可能源于MPNSTs复杂的异质性阻碍了药物研发——尽管许多MPNSTs与1型神经纤维瘤病（NF1）相关，该遗传性疾病由编码RAS负调控因子神经纤维瘤蛋白的NF1基因突变引起。当前MPNSTs新药研发方向已从单纯靶向RAS通路基因产物，转向激活免疫系统及调控其他驱动突变（如CDKN2A/B、SUZ12、EED和TP53）。本综述将阐述肉瘤治疗的最新进展及针对MPNSTs的药物研发前景。
肿瘤(癌症)患者之家