scholarly journals Histamine H4 receptor insights into a potential therapeutic target in breast cancer

10.2741/s420 ◽  
2015 ◽  
Vol 7 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Vanina A Medina
Keyword(s):  
Breast Cancer ◽  
Therapeutic Target ◽  
Potential Therapeutic Target ◽  
Histamine H4 Receptor ◽  
H4 Receptor

scholarly journals O28: M6A DEMETHYLASE FTO A POTENTIAL TARGET IN BRAIN METASTATIC BREAST CANCER

2021 ◽  
Vol 108 (Supplement_1) ◽  
Author(s):  
S Keelan ◽  
S Charmsaz ◽  
S Purcell ◽  
D Varešlija ◽  
S Cocchiglia ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Brain Metastasis ◽  
Disease Progression ◽  
Therapeutic Target ◽  
Disease Free Survival ◽  
Metastatic Breast ◽  
Potential Therapeutic Target ◽  
Rna Methylation ◽  
Pharmacological Inhibition

Abstract Introduction Brain metastasis (BrM) occurs in 10-30% of patients with advanced breast cancer (BC). BrM is increasing in incidence and confers a poor prognosis. We aimed to investigate the contribution of global epi-transcriptomic alterations in N6-methyladenosine (m6A) RNA-methylation as a therapeutic target in brain metastatic breast cancer. Method In preliminary studies we have demonstrated m6A demethylase – FTO as the main contributor to the progression of ER+ breast cancer. Furthermore an association between FTO and reduced disease-free-survival (n=870, p=0.018) was observed. Here we conducted an epigenetic inhibitor screen using two therapeutic agents, ethyl-ester-meclofenamic acid (MA2) and FB23-2 on matched 2D cell line, 3D organoid cultures and patient-derived xenografts (PDX) explant models of brain metastasis. Result Upon integration of mapped global RNA methylation landscape with matched proteomic analysis, we observed genome-wide RNA hypo-methylation of key pluripotency genes, including SOX2 and KLF4, as key players underlying tumour progression to the brain.  Genetic and pharmacological inhibition of FTO in novel ex vivo models of BrM significantly reduced protein expression levels of KLF4 and SOX2. Moreover, pharmacological inhibition of FTO with MA2 and FB23-2, inhibited cell proliferation in endocrine-resistant BC and patient BrM cells. We translate our findings to the clinic by demonstrating the efficacy of anti-FTO therapies in several unique PDX and 3D organoid BrM models. Conclusion Our results reveal epi-transcriptional remodelling events as a key mechanism in BrM. This study establishes an early role for targeting RNA methylation in the management of disease progression and presents FTO as a potential therapeutic target in BrM. Take-home message This study establishes an early role for targeting RNA methylation in the management of disease progression and presents FTO as a potential therapeutic target in brain metastatic breast cancer.

scholarly journals Stromal cells in breast cancer as a potential therapeutic target

Oncotarget ◽  
2018 ◽  
Vol 9 (34) ◽  
pp. 23761-23779 ◽  
Author(s):  
Samantha S. Dykes ◽  
Veronica S. Hughes ◽  
Jennifer M. Wiggins ◽  
Henrietta O. Fasanya ◽  
Mai Tanaka ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stromal Cells ◽  
Therapeutic Target ◽  
Potential Therapeutic Target

Histamine H4 receptor as a novel therapeutic target for the treatment of Leydig-cell tumours in prepubertal boys

2018 ◽  
Vol 91 ◽  
pp. 125-135 ◽  
Author(s):  
Adriana María Belén Abiuso ◽  
María Luisa Varela ◽  
Luis Haro Durand ◽  
Marcos Besio Moreno ◽  
Alejandra Marcos ◽  
...  
Keyword(s):  
Leydig Cell ◽  
Therapeutic Target ◽  
Histamine H4 Receptor ◽  
Prepubertal Boys ◽  
H4 Receptor ◽  
Leydig Cell Tumours ◽  
Novel Therapeutic

Impact of histamine H4 receptor deficiency on the modulation of T cells in a murine breast cancer model

2020 ◽  
Author(s):  
Melisa B. Nicoud ◽  
Mónica A. Táquez Delgado ◽  
María de la Paz Sarasola ◽  
Agustina Vidal ◽  
Daniela Speisky ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Cancer Model ◽  
Histamine H4 Receptor ◽  
Breast Cancer Model ◽  
H4 Receptor

c-Met as a potential therapeutic target in triple negative breast cancer

2020 ◽  
pp. 295-326
Author(s):  
Sapana Sameer Chaudhary ◽  
Sameer Choudhary ◽  
Sakshi Rawat ◽  
Gouri Ahir ◽  
Anwar L. Bilgrami ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Therapeutic Target ◽  
Triple Negative ◽  
Potential Therapeutic Target
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