scholarly journals Feedback Activation of Leukemia Inhibitory Factor Receptor Limits Response to Histone Deacetylase Inhibitors in Breast Cancer

Cancer Cell ◽  
2016 ◽  
Vol 30 (3) ◽  
pp. 459-473 ◽  
Author(s):  
Hanlin Zeng ◽  
Jia Qu ◽  
Nan Jin ◽  
Jun Xu ◽  
Chenchu Lin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Histone Deacetylase ◽  
Leukemia Inhibitory Factor ◽  
Histone Deacetylase Inhibitors ◽  
Inhibitory Factor ◽  
Leukemia Inhibitory Factor Receptor ◽  
Feedback Activation

scholarly journals Bevacizumab treatment of patients with breast cancer is associated with differential expression and up-regulation of the leukemia inhibitory factor receptor (LIFR).

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Leukemia Inhibitory Factor ◽  
Embryonic Stem ◽  
The United States ◽  
Inhibitory Factor ◽  
European Medicines Agency ◽  
The European Union ◽  
Leukemia Inhibitory Factor Receptor ◽  
Primary Tumors ◽  
Chemotherapeutic Regimen

Bevacizumab (Avastin) is an approved treatment option by the European Medicines Agency (1) for more than a quarter billion women in the European Union, and despite having its indication withdrawn by the Food and Drug Administration in 2011 is still utilized in clinical trials in the United States (2, 3). We mined published microarray data (4) from the PROMIX trial to understand in an unbiased fashion genes most transcriptionally perturbed by bevacizumab administration and how this interacted with a standard anthracycline and taxane chemotherapeutic regimen, epirubicin and docetaxel. We report here the differential and increased expression of the leukemia inhibitory factor receptor, a gateway to a signaling pathway required for the pluripotency of embryonic stem cells (5, 6), in the primary tumors of women treated with bevacizumab for breast cancer.

The role of the leukemia inhibitory factor receptor in embryo implantation and placentation

Placenta ◽  
2021 ◽  
Vol 114 ◽  
pp. 139
Author(s):  
Jumpei Terakawa ◽  
Kazuhiro Matsuo ◽  
Takafumi Namiki ◽  
Kana Ohtomo ◽  
Atsuko Kageyama ◽  
...  
Keyword(s):  
Leukemia Inhibitory Factor ◽  
Embryo Implantation ◽  
Inhibitory Factor ◽  
Leukemia Inhibitory Factor Receptor

scholarly journals Identification of brain metastasis genes and therapeutic evaluation of histone deacetylase inhibitors in a clinically relevant model of breast cancer brain metastasis

2018 ◽  
Author(s):  
Soo-Hyun Kim ◽  
Richard P. Redvers ◽  
Lap Hing Chi ◽  
Xiawei Ling ◽  
Andrew J. Lucke ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mammary Gland ◽  
Brain Metastasis ◽  
Histone Deacetylase ◽  
Clinical Relevance ◽  
Histone Deacetylase Inhibitors ◽  
Novel Therapies ◽  
Breast Cancer Brain Metastasis ◽  
The Brain

ABSTRACTBreast cancer brain metastasis remains largely incurable. While several mouse models have been developed to investigate the genes and mechanisms regulating breast cancer brain metastasis, these models often lack clinical relevance since they require the use of immune-compromised mice and/or are poorly metastatic to brain from the mammary gland. We describe the development and characterisation of an aggressive brain metastatic variant of the 4T1 syngeneic model (4T1Br4) that spontaneously metastasises to multiple organs, but is selectively more metastatic to the brain from the mammary gland than parental 4T1 tumours. By immunohistochemistry, 4T1Br4 tumours and brain metastases display a triple negative phenotype, consistent with the high propensity of this breast cancer subtype to spread to brain. In vitro assays indicate that 4T1Br4 cells have an enhanced ability to adhere to or migrate across a brain-derived endothelial monolayer and greater invasive response to brain-derived soluble factors compared to 4T1 cells. These properties are likely to contribute to the brain-selectivity of 4T1Br4 tumours. Expression profiling and gene set enrichment analyses demonstrate the clinical relevance of the 4T1Br4 model at the transcriptomic level. Pathway analyses implicate tumour-intrinsic immune regulation and vascular interactions in successful brain colonisation, revealing potential therapeutic targets. Evaluation of two histone deacetylase inhibitors, SB939 and 1179.4b, shows partial efficacy against 4T1Br4 metastasis to brain and other sites in vivo and potent radio-sensitising properties in vitro. The 4T1Br4 model provides a clinically relevant tool for mechanistic studies and to evaluate novel therapies against brain metastasis.SUMMARY STATEMENTWe introduce a new syngeneic mouse model of spontaneous breast cancer brain metastasis, demonstrate its phenotypic, functional and transcriptomic relevance to human TNBC brain metastasis and test novel therapies.

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