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Targeting LIF/LIFR signaling in cancer

Suryavathi Viswanadhapalli1,2, Kalarickal V Dileep3, Kam Y J Zhang3

  • 1Department of Obstetrics and Gynecology, University of Texas Health San Antonio, San Antonio, TX 78229, USA.

Genes & Diseases
|June 10, 2022
PubMed

Insights

Leukemia inhibitory factor (LIF) and its receptor (LIFR) drive cancer growth and resistance. Targeting the LIF/LIFR axis with agents like MSC-1 shows promise for cancer therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Signaling

Background:

  • Leukemia inhibitory factor (LIF) and its receptor (LIFR) are frequently overexpressed in solid tumors.
  • The LIF/LIFR axis activates key oncogenic pathways such as JAK/STAT3, MAPK, AKT, and mTOR.
  • Overexpression of LIF and autocrine LIF/LIFR signaling correlate with poor relapse-free survival and influence the tumor microenvironment.

Purpose of the Study:

  • To review the significance of the LIF/LIFR pathway in cancer.
  • To discuss inhibitors targeting the LIF/LIFR axis for cancer treatment.

Main Methods:

  • Literature review of studies on LIF/LIFR signaling in solid cancers.
  • Analysis of preclinical and clinical data for LIF and LIFR inhibitors.

Main Results:

  • LIF/LIFR signaling promotes tumor growth, metastasis, stemness, and therapy resistance.
  • Targeted agents, including the anti-LIF antibody MSC-1 and LIFR inhibitor EC359, have demonstrated efficacy in preclinical models.
  • Clinical trials with MSC-1 are currently underway.

Conclusions:

  • The LIF/LIFR axis is a critical driver of cancer progression and a viable therapeutic target.
  • Inhibitors disrupting LIF/LIFR signaling represent a promising strategy for novel cancer therapies.
Keywords:
AKT, protein kinase BHER2, human epidermal growth factor receptor 2JAK, Janus kinaseLIFLIF receptor, (LIFR)LIFRLIFR inhibitorSTAT3Targeted therapybreast cancer, (BCa)cancer stem cells, (CSCs)cardiotrophin 1, (CTF1)ciliary neurotrophic factor, (CNTF)colorectal cancer, (CRC)endometrial cancer, (ECa)humanized Anti-LIF antibody, (MSC-1)leukemia inhibitory factor, (LIF)mammalian target of rapamycin, (mTOR)mitogen activated protein kinase, (MAPK)oncostatin M, (OSM)ovarian cancer, (OCa)pancreatic ductal adenocarcinoma, (PDAC)programmed death-ligand 1, (PD-L1)prostate cancer, (PCa)signal transducer and activator of transcription 3, (STAT3)triple negative breast cancer, (TNBC)tumor micro environment, (TME)

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