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Review Article | Open Access

Targeting LIF/LIFR signaling in cancer

Suryavathi Viswanadhapallia,d, Kalarickal V. Dileepb, Kam Y.J. Zhangb, Hareesh B. Nairc, Ratna K. Vadlamudia,d( )
Department of Obstetrics and Gynecology, University of Texas Health San Antonio, San Antonio, TX 78229, USA
Laboratory for Structural Bioinformatics, Center for Biosystems Dynamics Research, RIKEN, Yokohama, Kanagawa 230-0045, Japan
Evestra, Inc., San Antonio, TX 78245, USA
Mays Cancer Center, University of Texas Health San Antonio, San Antonio, TX 78229, USA
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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.

Keywords

Targeted therapyLIFSTAT3LIFRLIFR inhibitor

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Genes & Diseases
Volume 9 Issue 4,
July 2022
Pages 973-980
DOI: 10.1016/j.gendis.2021.04.003
Cite this article:
Viswanadhapalli S, Dileep KV, Zhang KY, et al. Targeting LIF/LIFR signaling in cancer. Genes & Diseases, 2022, 9(4): 973-980. https://doi.org/10.1016/j.gendis.2021.04.003

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Received: 07 January 2021
Revised: 05 April 2021
Accepted: 09 April 2021
Published: 29 April 2021
© 2021, Chongqing Medical University.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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