Department of Medicine, Mayo Clinic, Jacksonville, FL, USA.
Department of Medicine, Division of Hematology Oncology, Mayo Clinic, Jacksonville, FL USA.
Expert Opin Investig Drugs. 2023 May;32(5):387-399. doi: 10.1080/13543784.2023.2206558. Epub 2023 Apr 24.
The Leukemia Inhibitory Factor (LIF) is a member of the interleukin-6 (IL-6) cytokine family. Known to induce differentiation of myeloid leukemia cells, evidence has accumulated supporting its role in cancer evolution through regulating cell differentiation, renewal, and survival. LIF has recently emerged as a biomarker and therapeutic target for pancreatic ductal adenocarcinoma (PDAC). The first in-human clinical trial has shown promising safety profile and has suggested a potential role for LIF inhibitor in combination regimen.
Herein, we summarize, discuss, and give an expert opinion on the role of LIF in PDAC promotion, and its potential role as a biomarker and target of anti-cancer therapy. We conducted an exhaustive PubMed search for English-language articles published from 1 January 1970, to 1 August 2022.
PDAC carries a devastating prognosis for patients, highlighting the need for advancing drug development. The results of the phase 1 trial with MSC-1 demonstrated tolerability and safety but modest efficacy. Future research should focus on investigating LIF targets in combination with current standard-of-care chemotherapy, and immunotherapy can be a promising approach. Further, larger multicenter clinical trials are needed to define the use of LIF as a new biomarker in PDAC patients.
白血病抑制因子(LIF)是白细胞介素-6(IL-6)细胞因子家族的一员。已知其可诱导髓系白血病细胞分化,有证据表明它通过调节细胞分化、更新和存活在癌症演变中发挥作用。LIF 最近已成为胰腺导管腺癌(PDAC)的生物标志物和治疗靶点。首例人体临床试验显示出良好的安全性,并表明 LIF 抑制剂联合方案可能具有一定作用。
本文总结、讨论并给出了专家意见,阐述了 LIF 在 PDAC 促进中的作用及其作为抗癌治疗的生物标志物和靶点的潜在作用。我们对 1970 年 1 月 1 日至 2022 年 8 月 1 日期间发表的英语文章进行了全面的 PubMed 搜索。
PDAC 患者预后极差,这凸显了推进药物开发的必要性。MSC-1 进行的 1 期试验结果表明其具有耐受性和安全性,但疗效中等。未来的研究应集中于研究 LIF 靶标与当前标准治疗化疗联合使用,免疫疗法可能是一种很有前途的方法。此外,还需要更大规模的多中心临床试验来确定将 LIF 用作 PDAC 患者的新生物标志物。