Estrogen receptor beta(ERβ) is one of the two key receptors(ERα, ERβ) that facilitate biological actions of 17β-estradiol(E2). ERβ is widely expressed in many tissues, and its expression is reduced or lost during...Estrogen receptor beta(ERβ) is one of the two key receptors(ERα, ERβ) that facilitate biological actions of 17β-estradiol(E2). ERβ is widely expressed in many tissues, and its expression is reduced or lost during progression of many tumors. ERβ facilitates estrogen signaling by both genomic(classical and non-classical) and extra-nuclear signaling. Emerging evidence suggests that ERβ functions as a tissue-specific tumor suppressor with anti-proliferative actions. Recent studies have identified a number of naturally available selective ERβ agonists. Targeting ERβ using its naturally available ligands is an attractive approach for treating and preventing cancers. This review presents the beneficial actions of ERβ signaling and clinical utility of several natural ERβ ligands as potential cancer therapy.展开更多
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...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.展开更多
基金supported by a Pre-doctoral Fellowship from the American Heart Association to ELS.(12PRE11530009)a Research Grant from the National Institute of Neurological Disorders and StrokeNational Institutes of Health,USA to DWB(NS050730)
基金supported by the NIH/NCI grant CA178499-01(RKV)CPRIT Training grant RP140105(GRS)2014-15 ABTA Discovery grant(GRS)
文摘Estrogen receptor beta(ERβ) is one of the two key receptors(ERα, ERβ) that facilitate biological actions of 17β-estradiol(E2). ERβ is widely expressed in many tissues, and its expression is reduced or lost during progression of many tumors. ERβ facilitates estrogen signaling by both genomic(classical and non-classical) and extra-nuclear signaling. Emerging evidence suggests that ERβ functions as a tissue-specific tumor suppressor with anti-proliferative actions. Recent studies have identified a number of naturally available selective ERβ agonists. Targeting ERβ using its naturally available ligands is an attractive approach for treating and preventing cancers. This review presents the beneficial actions of ERβ signaling and clinical utility of several natural ERβ ligands as potential cancer therapy.
基金This work was supported by the DOD BCRP (No. W81XWH-18-1-0016 (R.K.V)W81XWH-18-1-0015 (H.B.N)+2 种基金NCI R44CA235991 (H.B.N))NCI Cancer Center Support (No. P30CA054174-17)Elsa U. Pardee foundation (No. 166675-44096 (S.V), NIH (No. 1R01CA179120-01 (R.K.V)).Acknow。
文摘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.
