白血病抑制因子(LIF),和它的受体(LIFR),在许多实体癌中通常过表达,最近的研究表明LIF/LIFR轴是癌症治疗的有希望的临床靶标。LIF/LIFR激活致癌信号通路,包括JAK/STAT3作为即时效应子和MAPK,AKT,mTOR进一步下游。LIF/LIFR信号在肿瘤生长中起关键作用,programming,转移,干性和治疗抗性。许多实体癌显示LIF的过表达和LIF/LIFR轴的自分泌刺激;这些与较差的无复发生存率相关。LIF/LIFR信号传导还在调节肿瘤微环境(TME)中存在的多种免疫细胞类型中起作用。最近,两种靶向LIF(人源化抗LIF抗体,MSC-1)和LIFR抑制剂(EC359)正在开发中。两种药剂在临床前模型中显示出有效性,并且使用MSC-1抗体的临床试验正在进行中。本文综述了LIF/LIFR途径和破坏这一过程的抑制剂在癌症治疗中的意义。
Leukemia inhibitory factor (LIF), and its receptor (LIFR), are commonly over-expressed in many solid cancers and recent studies have implicated LIF/LIFR axis as a promising clinical target for cancer therapy. LIF/LIFR activate oncogenic signaling pathways including JAK/STAT3 as immediate effectors and MAPK, AKT, mTOR further downstream. LIF/LIFR signaling plays a key role in tumor growth, progression, metastasis, stemness and therapy resistance. Many solid cancers show overexpression of LIF and autocrine stimulation of the LIF/LIFR axis; these are associated with a poorer relapse-free survival. LIF/LIFR signaling also plays a role in modulating multiple immune cell types present in tumor micro environment (TME). Recently, two targeted agents that target LIF (humanized anti-LIF antibody, MSC-1) and LIFR inhibitor (EC359) were under development. Both agents showed effectivity in preclinical models and clinical trials using MSC-1 antibody are in progress. This article reviews the significance of LIF/LIFR pathways and inhibitors that disrupt this process for the treatment of cancer.