{Reference Type}: Journal Article
{Title}: Targeting LIF/LIFR signaling in cancer.
{Author}: Viswanadhapalli S;Dileep KV;Zhang KYJ;Nair HB;Vadlamudi RK;
{Journal}: Genes Dis
{Volume}: 9
{Issue}: 4
{Year}: Jul 2022
{Factor}: 7.243
{DOI}: 10.1016/j.gendis.2021.04.003
{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.