Targeting LIF/LIFR signaling in cancer

Suryavathi Viswanadhapalli; Kalarickal V. Dileep; Kam Y.J. Zhang; Hareesh B. Nair; Ratna K. Vadlamudi

doi:10.1016/j.gendis.2021.04.003

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Targeting LIF/LIFR signaling in cancer

更新时间：2022-06-24

- Targeting LIF/LIFR signaling in cancer
- Genes & Diseases Vol. 9, Issue 4, (2022)
- 作者机构：
  
  1. Department of Obstetrics and Gynecology, University of Texas Health San Antonio,TX,San Antonio,USA,78229
  2. Mays Cancer Center, University of Texas Health San Antonio,TX,San Antonio,USA,78229
  3. Laboratory for Structural Bioinformatics, Center for Biosystems Dynamics Research, RIKEN, Yokohama,Kanagawa,Japan,230-0045
  4. Evestra, Inc.,TX,San Antonio,USA,78245
- 作者简介：
- 基金信息：
- DOI：10.1016/j.gendis.2021.04.003
  CLC：
- Published：2022，
  
  Published Online：1 July 2022，
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Suryavathi Viswanadhapalli, Kalarickal V. Dileep, Kam Y.J. Zhang, et al. Targeting LIF/LIFR signaling in cancer. [J]. Genes & Diseases 9(4).(2022)
DOI：

Suryavathi Viswanadhapalli, Kalarickal V. Dileep, Kam Y.J. Zhang, et al. Targeting LIF/LIFR signaling in cancer. [J]. Genes & Diseases 9(4).(2022) DOI： 10.1016/j.gendis.2021.04.003.

摘要

Abstract

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.

关键词

Keywords

LIFLIFRLIFR inhibitorSTAT3Targeted therapy

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