Microenvironment and Metastasis Laboratory, Molecular Oncology Program, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
Center for Cancer and Blood Disorders, Children's National Medical Center, Washington, DC.
Clin Cancer Res. 2022 Aug 2;28(15):3185-3195. doi: 10.1158/1078-0432.CCR-21-3760.
Malignant peripheral nerve sheath tumors (MPNST) are aggressive soft-tissue sarcomas that represent an important clinical challenge, particularly given their strong tendency to relapse and metastasize and their relatively poor response to conventional therapies. To date, targeted, noncytotoxic treatments have demonstrated limited clinical success with MPNSTs, highlighting the need to explore other key pathways to find novel, improved therapeutic approaches. Here, we review evidence supporting the crucial role of the RAS/MEK/ERK pathway and angiogenesis in MPNST pathogenesis, and we focus on the potential of therapies targeting these pathways to treat this disease. We also present works suggesting that the combination of MEK inhibitors and antiangiogenic agents could represent a promising therapeutic strategy to manage MPNSTs. In support of this notion, we discuss the preclinical rational and clinical benefits of this combination therapy in other solid tumor types. Finally, we describe other emerging therapeutic approaches that could improve patient outcomes in MPNSTs, such as immune-based therapies.
恶性外周神经鞘瘤（MPNST）是一种侵袭性软组织肉瘤，是一个重要的临床挑战，特别是考虑到它们强烈的复发和转移倾向，以及对传统疗法相对较差的反应。迄今为止，针对 MPNST 的靶向、非细胞毒性治疗仅取得了有限的临床成功，这凸显了需要探索其他关键途径，以寻找新的、改进的治疗方法。在这里，我们回顾了支持 RAS/MEK/ERK 通路和血管生成在 MPNST 发病机制中的关键作用的证据，并重点关注针对这些通路的治疗方法治疗这种疾病的潜力。我们还介绍了一些研究工作，这些工作表明 MEK 抑制剂和抗血管生成药物的联合治疗可能是治疗 MPNST 的一种很有前途的治疗策略。为了支持这一观点，我们讨论了这种联合治疗在其他实体肿瘤类型中的临床前合理性和临床获益。最后，我们描述了其他可能改善 MPNST 患者预后的新兴治疗方法，例如免疫疗法。
