Abstract P6-07-06: Clinicopathologic characterization and comprehensive genomic profiling (CGP) of advanced breast cancer patients with fibroblast growth factor receptor (FGFR) alterations

2016 ◽  
Author(s):  
RH Alvarez ◽  
JW Thomas ◽  
K Kramer ◽  
J Niu ◽  
E Ahn ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Cancer Patients ◽  
Fibroblast Growth Factor Receptor ◽  
Growth Factor Receptor ◽  
Genomic Profiling ◽  
Fibroblast Growth ◽  
Breast Cancer Patients ◽  
Comprehensive Genomic Profiling

scholarly journals Targeted Inhibition of Fibroblast Growth Factor Receptor 1-GLI Through AZD4547 and GANT61 Modulates Breast Cancer Progression

2021 ◽  
Vol 9 ◽  
Author(s):  
Syeda Kiran Riaz ◽  
Walizeb Khan ◽  
Fen Wang ◽  
Tanwir Khaliq ◽  
Amber Malik ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Growth Factor ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Fibroblast Growth Factor Receptor ◽  
Growth Factor Receptor ◽  
Fibroblast Growth ◽  
Breast Cancer Patients ◽  
Shh Pathway

The underlying mechanism of fibroblast growth factor receptor 1 (FGFR1) mediated carcinogenesis is still not fully understood. For instance, FGFR1 upregulation leads to endocrine therapy resistance in breast cancer patients. The current study aimed to identify FGFR1-linked genes to devise improved therapeutic strategies. RNA-seq and microarray expression data of 1,425 breast cancer patients from two independent cohorts were downloaded for the analysis. Gene Set Enrichment Analysis (GSEA) was performed to identify differentially expressed pathways associated with FGFR1 expression. Validation was done using 150 fresh tumor biopsy samples of breast cancer patients. The clinical relevance of mRNA and protein expression of FGFR1 and its associated genes were also evaluated in mouse embryonic fibroblasts (MEFs) and breast cancer cell line (MDA-MB-231). Furthermore, MDA-MB-231 cell line was treated with AZD4547 and GANT61 to identify the probable role of FGFR1 and its associated genes on cells motility and invasion. According to GSEA results, SHH pathway genes were significantly upregulated in FGFR1 patients in both discovery cohorts of breast cancer. Statistical analyses using both discovery cohorts and 150 fresh biopsy samples revealed strong association of FGFR1 and GLI1, a member of SHH pathway. The increase in the expression of these molecules was associated with poor prognosis, lymph node involvement, late stage, and metastasis. Combined exposures to AZD4547 (FGFR1 inhibitor) and GANT61 (GLI1 inhibitor) significantly reduced cell proliferation, cell motility, and invasion, suggesting molecular crosstalk in breast cancer progression and metastasis. A strong positive feedback mechanism between FGFR1–GLI1 axis was observed, which significantly increased cell proliferation and metastasis. Targeting FGFR1–GLI1 simultaneously will significantly improve the prognosis of breast cancer in patients.

scholarly journals Current Status of Fibroblast Growth Factor Receptor-Targeted Therapies in Breast Cancer

Cells ◽  
2018 ◽  
Vol 7 (7) ◽  
pp. 76 ◽  
Author(s):  
Navid Sobhani ◽  
Anna Ianza ◽  
Alberto D’Angelo ◽  
Giandomenico Roviello ◽  
Fabiola Giudici ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor Receptor ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Tumor Formation ◽  
Current Status ◽  
Fibroblast Growth ◽  
Fibroblast Growth Factor Receptors

Breast cancer (BC) is the most common malignancy and second only to lung cancer in terms of mortality in women. Despite the incredible progress made in this field, metastatic breast cancer has a poor prognosis. In an era of personalized medicine, there is an urgent need for better knowledge of the biology leading to the disease, which can lead to the design of increasingly accurate drugs against patients’ specific molecular aberrations. Among one of the actionable targets is the fibroblast growth factor receptor (FGFR) pathway, triggered by specific ligands. The Fibroblast Growth Factor Receptors/Fibroblast Growth Factors (FGFRs/FGFs) axis offers interesting molecular targets to be pursued in clinical development. This mini-review will focus on the current knowledge of FGFR mutations, which lead to tumor formation and summarizes the state-of-the-art therapeutic strategies for targeted treatments against the FGFRs/FGFs axis in the context of BC.

Altered intracellular localization of fibroblast growth factor receptor 3 in human breast cancer

2001 ◽  
Vol 194 (1) ◽  
pp. 27-34 ◽  
Author(s):  
Charles Zammit ◽  
Richard Barnard ◽  
Jennifer Gomm ◽  
Rebecca Coope ◽  
S. Shousha ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Human Breast Cancer ◽  
Fibroblast Growth Factor Receptor ◽  
Intracellular Localization ◽  
Growth Factor Receptor ◽  
Fibroblast Growth ◽  
Human Breast

Targeting fibroblast growth factor receptor in breast cancer: a promise or a pitfall?

2014 ◽  
Vol 18 (6) ◽  
pp. 665-678 ◽  
Author(s):  
Francesca Bedussi ◽  
Alberto Bottini ◽  
Maurizio Memo ◽  
Stephen B Fox ◽  
Sandra Sigala ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor Receptor ◽  
Growth Factor Receptor ◽  
Fibroblast Growth

scholarly journals Fibroblast growth factor receptor 4 (FGFR4) and fibroblast growth factor 19 (FGF19) autocrine enhance breast cancer cells survival

Oncotarget ◽  
2016 ◽  
Vol 7 (36) ◽  
pp. 57633-57650 ◽  
Author(s):  
Kai Hung Tiong ◽  
Boon Shing Tan ◽  
Heng Lungh Choo ◽  
Felicia Fei-Lei Chung ◽  
Ling-Wei Hii ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Cancer Cells ◽  
Fibroblast Growth Factor ◽  
Breast Cancer Cells ◽  
Fibroblast Growth Factor Receptor ◽  
Growth Factor Receptor ◽  
Fibroblast Growth ◽  
Fibroblast Growth Factor 19

scholarly journals Impact of fibroblast growth factor receptor 1 (FGFR1) amplification on the prognosis of breast cancer patients

2020 ◽  
Vol 184 (2) ◽  
pp. 311-324
Author(s):  
Ramona Erber ◽  
Matthias Rübner ◽  
Simon Davenport ◽  
Sven Hauke ◽  
Matthias W. Beckmann ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor Receptor ◽  
Statistical Significance ◽  
Growth Factor Receptor ◽  
Small Sample ◽  
Fibroblast Growth ◽  
Luminal B ◽  
The Impact

Abstract Purpose Various aberrations in the fibroblast growth factor receptor genes FGFR1, FGFR2, and FGFR3 are found in different cancers, including breast cancer (BC). This study analyzed the impact of FGFR amplification on the BC prognosis. Methods The study included 894 BC patients. The amplification rates of FGFR1, FGFR2, and FGFR3 were evaluated on tissue microarrays using fluorescence in situ hybridization (FISH). Associations between these parameters and prognosis were analyzed using multivariate Cox regression analyses. Results FGFR1 FISH was assessable in 503 samples, FGFR2 FISH in 447, and FGFR3 FISH in 562. The FGFR1 amplification rate was 6.6% (n = 33). Increased FGFR2 copy numbers were seen in 0.9% (n = 4); only one patient had FGFR3 amplification (0.2%). Most patients with FGFR1 amplification had luminal B-like tumors (69.7%, n = 23); only 32.6% (n = 153) of patients without FGFR1 amplification had luminal B-like BC. Other patient and tumor characteristics appeared similar between these two groups. Observed outcome differences between BC patients with and without FGFR1 amplification did not achieve statistical significance; however, there was a trend toward poorer distant metastasis-free survival in BC patients with FGFR1 amplification (HR = 2.08; 95% CI 0.98 to 4.39, P = 0.05). Conclusion FGFR1 amplification occurs most frequently in patients with luminal B-like BC. The study showed a nonsignificant correlation with the prognosis, probably due to the small sample size. Further research is therefore needed to address the role of FGFR1 amplifications in early BC patients. FGFR2 and FGFR3 amplifications are rare in patients with primary BC.

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