Deciphering role of FGFR signalling pathway in pancreatic cancer

Kang, Xiaodiao; Zeng, Lin; Xu, Minhui; Pan, Jun; Wang, Zhiwei

doi:10.1111/cpr.12605

Cited by 42 publications

(37 citation statements)

References 144 publications

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“…FGFR genes are involved in multiple biological processes, including cell transformation, angiogenesis, apoptosis, embryonic development, and tissue repair. Mutations and ampliﬁcation of FGFR gene members have been shown to serve as therapeutic targets in a wide range of human malignancies, such as gastric, lung, and bladder cancers 18,19. Previous studies have demonstrated that overexpression of FGFR fusion proteins promotes tumor cell proliferation and migration 20.…”

Section: Discussionmentioning

confidence: 99%

FGFR2-BICC1: A Subtype Of FGFR2 Oncogenic Fusion Variant In Cholangiocarcinoma And The Response To Sorafenib

Xiao

Wang

et al. 2019

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Fibroblast growth factor receptor (FGFR) family includes four highly conserved receptor tyrosine kinases. Particularly, FGFR2 has been identified as a potential target for tyrosine kinase inhibitor (TKI) treatment. Except for immunohistochemistry and fluorescence in situ hybridization, next-generation sequencing (NGS) technology represents a novel tool for FGFR2 detection that covers a wide range of fusion genes. In the present work, we present a case of cholangiocarcinoma who had FGFR2-BICC1 rearrangement detected by NGS. A 76-year-old female diagnosed with cholangiocarcinoma underwent four cycles of chemotherapy. The NGS assay showed that the tumor had a FGFR2-BICC1 rearrangement. The patient had a favorable tumor response to sorafenib. Herein, we report the first case with cholangiocarcinoma harboring FGFR2-BICC1 who is sensitive to sorafenib therapy.

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Section: Discussionmentioning

confidence: 99%

FGFR2-BICC1: A Subtype Of FGFR2 Oncogenic Fusion Variant In Cholangiocarcinoma And The Response To Sorafenib

Xiao

Wang

et al. 2019

OTT

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“…Furthermore, smoking, alcohol abuse, and a high fat and protein diet increase the risk of developing PDAC, underlining the crucial role of inflammation in pancreatic carcinogenesis which is characterized by desmoplasia-driven activation and differentiation of pancreatic stellate cells into pancreatic αSMA+/vimentin+ myofibroblasts [11][12][13]. Beside the systemic inflammatory response (SIR), emerging evidence determined that inflammation-associated vital genes, signaling pathways, and growth factors such as PI3K (phosphatidylinositol), Ras-MAPK (mitogen-activated protein kinase), STAT (signal and activator of transcription), Wnt, EGF (epidermal growth factor), and FGF (fibroblast growth factor) are involved in the carcinogenesis and progression of PDAC [14][15][16][17][18][19][20][21]. FGFs are peptide-like molecules which bind to their specific receptors (FGFR) on cell membranes to govern cell growth.…”

Section: Original Articlementioning

confidence: 99%

“…In mammals, 22 different FGFs are known today. Beside the biggest FGF subfamily, the canonical FGFs, one endocrine and one intracellular FGF subfamily exists and all FGFs mediate their cellular response via binding and activation of one of four FGFRs [14,21]. A broad range of FGFs have been investigated in vitro and in vivo for their role and influence on PDAC, including the treatment response of pancreatic cancer cells to chemotherapy and the use of anti-FGF therapy, so called "ligand-traps" [14,[22][23][24][25][26][27][28][29].…”

Section: Original Articlementioning

confidence: 99%

Fibroblast growth factor 8 overexpression is predictive of poor prognosis in pancreatic ductal adenocarcinoma

et al. 2020

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Summary Background Despite distinctive advances in the field of pancreatic cancer therapy over the past few years, patient survival remains poor. Fibroblast growth factors 8 (FGF8) and 18 (FGF18) both play a role in modulating the activity of malignant cells and have been identified as promising biomarkers in a number of cancers. However, no data exist on the expression of FGF8 and FGF18 in pancreatic ductal adenocarcinoma (PDAC). Methods Protein expression levels of FGF8 and FGF18 in postoperative specimens of neoadjuvantly treated and primarily resected patients were investigated using immunohistochemistry. Immunostaining scores were calculated as the products of the staining intensity and the staining rate. Scores exceeding the median score were considered as high expression. Results Specimens from 78 patients with PDAC were available and met the eligibility criteria for analysis of protein expression using immunohistochemistry. 15 (19.2%) patients had received neoadjuvant chemotherapy. High protein levels of FGF8 and FGF18 were detected in 40 (51.8%) and 33 (42.3%) patients, respectively. Kaplan–Meier analysis demonstrated significantly shorter overall survival in patients with high expression of FGF8 (p = 0.04). Multivariable Cox proportional hazard regression models revealed that high expression of FGF8 (Hazard ratio [HR] 0.53, 95% Confidence interval [CI] 0.32–0.89, p = 0.016) was an independent prognostic factor for diminished overall survival in patients with PDAC. By contrast, no statistical significance was found for FGF18 overexpression. In addition, the FGF8 protein level correlated with the factor resection margin (p = 0.042). Conclusion FGF8 is a promising target for new anticancer therapies using FGF inhibitors in pancreatic ductal adenocarcinomas.

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“…However, this novel regulatory switch does not target the CDH1 promoter. The external cues that turn this switch on include fibroblast growth factor (FGF)‐2 that is abundantly present in the tumor microenvironment 37,38 . Therefore, this regulatory switch could contribute to the phenotypic plasticity of cancer cells during malignant progression.…”

Section: Introductionmentioning

confidence: 99%

ZEB1 and oncogenic Ras constitute a regulatory switch for stimulus‐dependent E‐cadherin downregulation

et al. 2020

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E-cadherin, encoded by the CDH1 gene, is a calcium-dependent cell adhesion molecule localized in adherens junctions of epithelial cells. 1 The downregulation of E-cadherin expression is considered one of the hallmarks of cells undergoing epithelial-mesenchymal transition (EMT) and is closely associated with cell invasion. It has been reported that interference of E-cadherin function by neutralizing antibodies results in the acquirement of invasive properties by nontransformed epithelial cells. 2 Moreover, an inverse correlation between invasiveness and E-cadherin expression level was observed in various human carcinoma cell lines, and the invasiveness of E-cadherin-negative cancer cells was prevented by its exogenous expression. 3 E-cadherin is also a putative tumor suppressor as it suppresses the progression from adenoma to carcinoma 4 and is involved in contact inhibition, thereby suppressing excessive cell growth. 5 Furthermore, its downregulation facilitates immune escape 6 and leads to drug resistance in epidermal growth factor receptor-mutated cancer cells. 7 Consistently, loss of E-cadherin expression is often detected in invasive cancer cells and correlates with a poor prognosis in some

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Deciphering role of FGFR signalling pathway in pancreatic cancer

Cited by 42 publications

References 144 publications

<p><em>FGFR2-BICC1</em>: A Subtype Of <em>FGFR2</em> Oncogenic Fusion Variant In Cholangiocarcinoma And The Response To Sorafenib</p>

<p><em>FGFR2-BICC1</em>: A Subtype Of <em>FGFR2</em> Oncogenic Fusion Variant In Cholangiocarcinoma And The Response To Sorafenib</p>

Fibroblast growth factor 8 overexpression is predictive of poor prognosis in pancreatic ductal adenocarcinoma

ZEB1 and oncogenic Ras constitute a regulatory switch for stimulus‐dependent E‐cadherin downregulation

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