Associated expressions of FGFR-2 and FGFR-3: from mouse mammary gland physiology to human breast cancer

Cerliani, Juan P.; Vanzulli, Silvia I.; Piñero, Cecilia Pérez; Bottino, María Cecilia; Sahores, Ana; Núñez, Margarita Ostrowski de; Varchetta, Romina; Martins, Rubén; Zeitlin, Eduardo; Hewitt, Stephen M.; Molinolo, Alfredo A.; Lanari, Claudia; Lamb, Caroline A.

doi:10.1007/s10549-011-1883-6

Cited by 24 publications

(18 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It has been described that in hormone-related cancers, members of FGF family can play key roles in acquisition of hormone independence (31). Moreover, in endometrial tumorigenesis, FGFR2-activated mutations occur in type I ECC, which are estrogen-related carcinomas.…”

Section: Dovitinib Treatment Increase Era Expression In Fgfr2-activatmentioning

confidence: 99%

Combinatorial Therapy Using Dovitinib and ICI182.780 (Fulvestrant) Blocks Tumoral Activity of Endometrial Cancer Cells

Eritja

Domingo

Dosil

et al. 2014

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

Mutations in fibroblast growth factor receptor 2 (FGFR2) have been recently described as a molecularspecific feature in endometrial carcinomas and the presence of activated FGFR2 mutations is associated with poor prognosis. For that reason, inhibition of FGFR2 could be a therapeutic target in the treatment of endometriod carcinomas. In this work, we investigated the antitumoral activity of dovitinib (a multiple kinase inhibitor) in human endometrial cancer cell (ECC) lines. We found that dovitinib caused cell growth arrest, loss of clonogenic growth, and cell-cycle arrest in FGFR2-mutated ECCs in in vitro and in vivo experiments. Next, we investigated the mechanistic basis of dovitinib effects. We could determine that dovitinib modified expression levels of well-known key cell-cycle regulatory proteins that induce cellular senescence. To further investigate the role of dovitinib, we analyzed its effect on estrogen receptor a (ER-a) expression. Surprisingly, we discovered that dovitinib enhances ER-a expression in FGFR2-mutant ECCs. Because blocking one signaling pathway is often not sufficient to cause total tumor regression and the effectiveness of individual inhibitors is often short-lived, we examined the impact of targeting FGFR2 with dovitinib in combination with a selective ER antagonist, fulvestrant (ICI182.780). Combination of dovitinib plus ICI182.780 resulted in a significantly higher inhibition of cell growth than dovitinib treatment alone. These findings suggest that combinatory therapies using dovitinib plus ICI182.780 treatment can be truly effective in patients with endometrial carcinomas carrying FGFR2 mutations. Mol Cancer Ther; 13(4); 776-87. Ó2014 AACR.

show abstract

Section: Dovitinib Treatment Increase Era Expression In Fgfr2-activatmentioning

confidence: 99%

Combinatorial Therapy Using Dovitinib and ICI182.780 (Fulvestrant) Blocks Tumoral Activity of Endometrial Cancer Cells

Eritja

Domingo

Dosil

et al. 2014

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

show abstract

“…Another example includes FGFR3 and FGFR4 that are known to be associated with breast cancer as revealed in [37]. Table 5 summarizes the top 5 hub methylation features and their subtype-specific degrees along with the supporting literature for the relevance of each feature in breast cancer.…”

Section: Resultsmentioning

confidence: 99%

Identifying subtype-specific associations between gene expression and DNA methylation profiles in breast cancer

et al. 2017

View full text Add to dashboard Cite

BackgroundBreast cancer is a complex disease in which different genomic patterns exists depending on different subtypes. Recent researches present that multiple subtypes of breast cancer occur at different rates, and play a crucial role in planning treatment. To better understand underlying biological mechanisms on breast cancer subtypes, investigating the specific gene regulatory system via different subtypes is desirable.MethodsGene expression, as an intermediate phenotype, is estimated based on methylation profiles to identify the impact of epigenomic features on transcriptomic changes in breast cancer. We propose a kernel weighted l1-regularized regression model to incorporate tumor subtype information and further reveal gene regulations affected by different breast cancer subtypes. For the proper control of subtype-specific estimation, samples from different breast cancer subtype are learned at different rate based on target estimates. Kolmogorov Smirnov test is conducted to determine learning rate of each sample from different subtype.ResultsIt is observed that genes that might be sensitive to breast cancer subtype show prediction improvement when estimated using our proposed method. Comparing to a standard method, overall performance is also enhanced by incorporating tumor subtypes. In addition, we identified subtype-specific network structures based on the associations between gene expression and DNA methylation.ConclusionsIn this study, kernel weighted lasso model is proposed for identifying subtype-specific associations between gene expressions and DNA methylation profiles. Identification of subtype-specific gene expression associated with epigenomic changes might be helpful for better planning treatment and developing new therapies.

show abstract

“…Indeed, increased expression of FGFR2 is associated with poor overall survival and disease-free survival [ 35 ]. Following the detection of FGFR2 and FGFR3 constitutive activation in hormone-independent murine mammary tumors, FGFR expression levels were determined in tumor samples from patients with breast cancer ( n = 58) [ 36 ]. This analysis detected a strong association between FGFR2 and FGFR3, with weaker associations between FGFR2 or FGFR3 and ER.…”

Section: Prognostic Significance Of Fgfr Aberrancymentioning

confidence: 99%

Rationale for targeting fibroblast growth factor receptor signaling in breast cancer

André

Cortés²

2015

Breast Cancer Res Treat

106

View full text Add to dashboard Cite

Fibroblast growth factor receptor (FGFR) signaling is involved in multiple biological processes, including cell proliferation, survival, differentiation, migration, and apoptosis during embryonic development and adult tissue homeostasis. Given its role in the activation of critical signaling pathways, aberrant FGFR signaling has been implicated in multiple cancer types. A comprehensive search of PubMed and congress abstracts was conducted to identify reports on FGFR pathway components in breast cancer. In breast cancers, FGFR1 and FGFR4 gene amplification and single nucleotide polymorphisms in FGFR2 and FGFR4 have been detected. Commonly, these FGFR aberrations and gene amplifications lead to increased FGFR signaling and have been linked with poor prognosis and resistance to breast cancer treatments. Here, we review the role of FGFR signaling and the impact of FGFR genetic amplifications/aberrations on breast tumors. In addition, we summarize the most recent preclinical and clinical data on FGFR-targeted therapies in breast cancer. Finally, we highlight the ongoing clinical trials of the FGFR-targeted agents dovitinib, AZD4547, lucitanib, BGJ398, and JNJ-42756493, which are selected for patients with FGFR pathway-amplified breast cancer. Aberrant FGFR pathway amplification may drive some breast cancers. Inhibition of FGFR signaling is being explored in the clinic, and data from these trials may refine our ability to select patients who would best respond to these treatments.

show abstract

Associated expressions of FGFR-2 and FGFR-3: from mouse mammary gland physiology to human breast cancer

Cited by 24 publications

References 46 publications

Combinatorial Therapy Using Dovitinib and ICI182.780 (Fulvestrant) Blocks Tumoral Activity of Endometrial Cancer Cells

Combinatorial Therapy Using Dovitinib and ICI182.780 (Fulvestrant) Blocks Tumoral Activity of Endometrial Cancer Cells

Identifying subtype-specific associations between gene expression and DNA methylation profiles in breast cancer

Rationale for targeting fibroblast growth factor receptor signaling in breast cancer

Contact Info

Product

Resources

About