Tremblay Douglas, Mesa Ruben
Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
UT Health San Antonio Cancer Center, San Antonio, TX, USA.
Curr Treat Options Oncol. 2023 Feb;24(2):61-75. doi: 10.1007/s11864-023-01052-9. Epub 2023 Jan 14.
Currently approved therapies for myelofibrosis (MF) consist of JAK inhibitors, which produce meaningful improvements in spleen size and symptom burden but do not significantly impact leukemic progression. In addition, many patients develop resistance or intolerance to existing therapies and are left without meaningful therapeutic options. There has been recent rapid development of agents in MF that may be able to fill these unmet needs. Importantly, most treatments currently in clinical development have targets outside the JAK-STAT pathway, including BET, BCL-2/BCL-xL, PI3k, HDM2, PIM-1, SINE, telomerase, LSD1, and CD123. These therapies are being tested in combination with JAK inhibitors in the front-line setting and in patients with a suboptimal response, as well as a single agent after JAK inhibitor failure. This next generation of agents is likely to produce a paradigm shift in MF treatment with a focus on combination treatment targeting multiple areas of MF pathophysiology.
目前获批用于治疗骨髓纤维化（MF）的疗法包括JAK抑制剂，这些抑制剂可使脾脏大小和症状负担得到显著改善，但对白血病进展没有显著影响。此外，许多患者对现有疗法产生耐药性或不耐受，从而没有有效的治疗选择。近年来，骨髓纤维化领域的药物发展迅速，可能能够满足这些未被满足的需求。重要的是，目前大多数处于临床开发阶段的治疗方法都针对JAK-STAT通路以外的靶点，包括BET、BCL-2/BCL-xL、PI3k、HDM2、PIM-1、SINE、端粒酶、LSD1和CD123。这些疗法正在一线治疗中与JAK抑制剂联合进行测试，用于治疗反应欠佳的患者，以及在JAK抑制剂治疗失败后作为单一药物进行测试。这一代新的药物可能会使骨髓纤维化的治疗模式发生转变，重点是针对骨髓纤维化病理生理学多个领域的联合治疗。
