Kuykendall Andrew T, Horvat Nathan P, Pandey Garima, Komrokji Rami, Reuther Gary W
Department of Malignant Hematology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.
Morsani College of Medicine, University of South Florida, Tampa, FL 33612 USA.
Cancers (Basel). 2020 Aug 14;12(8):2278. doi: 10.3390/cancers12082278.
Myelofibrosis (MF) is a myeloproliferative neoplasm hallmarked by the upregulation of the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway with associated extramedullary hematopoiesis and a high burden of disease-related symptoms. While JAK inhibitor therapy is central to the management of MF, it is not without limitations. In an effort to improve treatment for MF patients, there have been significant efforts to identify combination strategies that build upon the substantial benefits of JAK inhibition. Early efforts to combine agents with additive therapeutic profiles have given way to rationally designed combinations hoping to demonstrate clinical synergism and modify the underlying disease. In this article, we review the preclinical basis and existing clinical data for JAK inhibitor combination strategies while highlighting emerging strategies of particular interest.
骨髓纤维化（MF）是一种骨髓增殖性肿瘤，其特征是Janus激酶（JAK）-信号转导子和转录激活子（STAT）通路上调，伴有髓外造血及高负担的疾病相关症状。虽然JAK抑制剂疗法是MF治疗的核心，但并非没有局限性。为了改善对MF患者的治疗，人们付出了巨大努力来确定在JAK抑制的显著益处基础上的联合治疗策略。早期将具有相加治疗作用的药物联合使用的尝试，已让位于合理设计的联合方案，以期证明临床协同作用并改变潜在疾病。在本文中，我们回顾了JAK抑制剂联合治疗策略的临床前基础和现有临床数据，同时重点介绍了特别值得关注的新兴策略。
