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Targeting LIF/LIFR signaling in cancer

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 a...

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Detalles Bibliográficos
Autores principales: Viswanadhapalli, Suryavathi, Dileep, Kalarickal V., Zhang, Kam Y.J., Nair, Hareesh B., Vadlamudi, Ratna K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Chongqing Medical University 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9170604/
https://www.ncbi.nlm.nih.gov/pubmed/35685476
http://dx.doi.org/10.1016/j.gendis.2021.04.003
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author Viswanadhapalli, Suryavathi
Dileep, Kalarickal V.
Zhang, Kam Y.J.
Nair, Hareesh B.
Vadlamudi, Ratna K.
author_facet Viswanadhapalli, Suryavathi
Dileep, Kalarickal V.
Zhang, Kam Y.J.
Nair, Hareesh B.
Vadlamudi, Ratna K.
author_sort Viswanadhapalli, Suryavathi
collection PubMed
description 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.
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spelling pubmed-91706042022-06-08 Targeting LIF/LIFR signaling in cancer Viswanadhapalli, Suryavathi Dileep, Kalarickal V. Zhang, Kam Y.J. Nair, Hareesh B. Vadlamudi, Ratna K. Genes Dis Review Article 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. Chongqing Medical University 2021-04-29 /pmc/articles/PMC9170604/ /pubmed/35685476 http://dx.doi.org/10.1016/j.gendis.2021.04.003 Text en © 2021 Chongqing Medical University. Production and hosting by Elsevier B.V. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Review Article
Viswanadhapalli, Suryavathi
Dileep, Kalarickal V.
Zhang, Kam Y.J.
Nair, Hareesh B.
Vadlamudi, Ratna K.
Targeting LIF/LIFR signaling in cancer
title Targeting LIF/LIFR signaling in cancer
title_full Targeting LIF/LIFR signaling in cancer
title_fullStr Targeting LIF/LIFR signaling in cancer
title_full_unstemmed Targeting LIF/LIFR signaling in cancer
title_short Targeting LIF/LIFR signaling in cancer
title_sort targeting lif/lifr signaling in cancer
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9170604/
https://www.ncbi.nlm.nih.gov/pubmed/35685476
http://dx.doi.org/10.1016/j.gendis.2021.04.003
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