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.

白血病抑制因子 (LIF) 及其受体 (LIFR) 在许多实体癌中通常过度表达，最近的研究表明 LIF/LIFR 轴是癌症治疗的一个有前景的临床靶点。 LIF/LIFR 激活致癌信号通路，包括作为直接效应器的 JAK/STAT3 和下游的 MAPK、AKT、mTOR。 LIF/LIFR 信号在肿瘤生长、进展、转移、干细胞性和治疗耐药性中发挥着关键作用。许多实体癌表现出 LIF 的过度表达和 LIF/LIFR 轴的自分泌刺激；这些与较差的无复发生存率有关。 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发挥作用。最近，两种针对LIF（人源化抗LIF抗体，MSC-1）和LIFR抑制剂（EC359）的靶向药物正在开发中。两种药物均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。本文回顾了 LIF/LIFR 通路和破坏这一过程的抑制剂对于治疗癌症的重要性。