Targeting LIF/LIFR signaling in cancer

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

Research output: Contribution to journalReview articlepeer-review

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.

Original languageEnglish (US)
JournalGenes and Diseases
DOIs
StateAccepted/In press - 2021

Keywords

  • LIF
  • LIFR
  • LIFR inhibitor
  • STAT3
  • Targeted therapy

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics(clinical)
  • Cell Biology

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