Targeting fibroblast growth factor receptor (FGFR) pathway in renal cell carcinoma

Massari, Francesco; Ciccarese, Chiara; Santoni, Matteo; López-Beltrán, Antonio; Scarpelli, Marina; Montironi, Rodolfo; Liu, Cheng

doi:10.1586/14737140.2015.1110488

Cited by 22 publications

(14 citation statements)

References 32 publications

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“…These proteins are key players in cell proliferation, differentiation, and signaling pathways and have critical involvement in developmental processes. In addition, these proteins are also considered as potential targets for designing therapies against RCC1213.…”

Section: Resultsmentioning

confidence: 99%

Gene expression-based biomarkers for discriminating early and late stage of clear cell renal cancer

Bhalla

Chaudhary

Kumar

et al. 2017

Sci Rep

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In this study, an attempt has been made to identify expression-based gene biomarkers that can discriminate early and late stage of clear cell renal cell carcinoma (ccRCC) patients. We have analyzed the gene expression of 523 samples to identify genes that are differentially expressed in the early and late stage of ccRCC. First, a threshold-based method has been developed, which attained a maximum accuracy of 71.12% with ROC 0.67 using single gene NR3C2. To improve the performance of threshold-based method, we combined two or more genes and achieved maximum accuracy of 70.19% with ROC of 0.74 using eight genes on the validation dataset. These eight genes include four underexpressed (NR3C2, ENAM, DNASE1L3, FRMPD2) and four overexpressed (PLEKHA9, MAP6D1, SMPD4, C11orf73) genes in the late stage of ccRCC. Second, models were developed using state-of-art techniques and achieved maximum accuracy of 72.64% and 0.81 ROC using 64 genes on validation dataset. Similar accuracy was obtained on 38 genes selected from subset of genes, involved in cancer hallmark biological processes. Our analysis further implied a need to develop gender-specific models for stage classification. A web server, CancerCSP, has been developed to predict stage of ccRCC using gene expression data derived from RNAseq experiments.

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Section: Resultsmentioning

confidence: 99%

Gene expression-based biomarkers for discriminating early and late stage of clear cell renal cancer

Bhalla

Chaudhary

Kumar

et al. 2017

Sci Rep

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“…In addition, high levels of FGF-2 in plasma were associated with large tumor size in head and neck cancers [ 48 ] and with tumor growth kinetics in advanced colorectal cancer [ 49 ]. Increased basic-FGF plasma concentrations are also correlated with high tumor grade and stage, metastatic spreading, and poor prognosis in kidney cancer patients, thereby illustrating that fibroblast growth factor receptor (FGFR) pathway is an attractive therapeutic target for patients with renal cell carcinoma [ 50 ].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of FGF2-Mediated Signaling in GIST—Promising Approach for Overcoming Resistance to Imatinib

Boichuk

Galembikova

Mikheeva

et al. 2020

Cancers

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Inhibition of KIT-signaling is a major molecular target for gastrointestinal stromal tumor (GIST) therapy, and imatinib mesylate (IM) is known as the most effective first-line treatment option for patients with advanced, unresectable, and/or metastatic GISTs. We show here for the first time that the inhibition of KIT-signaling in GISTs induces profound changes in the cellular secretome, leading to the release of multiple chemokines, including FGF-2. IM increased migration, invasion, and colony formation of IM-resistant GISTs in an FGF2-dependent manner, whereas the use of blocking anti-FGF2 antibodies or BGJ398, a selective FGFR inhibitor, abolished these effects, thus suggesting that the activation of FGF2-mediated signaling could serve as a compensatory mechanism of KIT-signaling inhibited in GISTs. Conversely, FGF-2 rescued the growth of IM-naive GISTs treated by IM and protected them from IM-induced apoptosis, consistent with the possible involvement of FGF-2 in tumor response to IM-based therapy. Indeed, increased FGF-2 levels in serum and tumor specimens were found in IM-treated mice bearing IM-resistant GIST xenografts, whereas BGJ398 used in combination with IM effectively inhibited their growth. Similarly, increased FGF-2 expression in tumor specimens from IM-treated patients revealed the activation of FGF2-signaling in GISTs in vivo. Collectively, the continuation of IM-based therapy for IM-resistant GISTs might facilitate disease progression by promoting the malignant behavior of tumors in an FGF2-dependent manner. This provides a rationale to evaluate the effectiveness of the inhibitors of FGF-signaling for IM-resistant GISTs.

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“…Aberrant FGFR expression or gene mutations can contribute to the occurrence and development of various tumors [ 71 , 72 , 73 , 74 , 75 ]. Various studies have shown that the FGFR1 gene is over-amplified in lung cancer and estrogen receptor-positive breast cancer [ 76 , 77 , 78 ], FGFR2 overexpression is related to diffuse gastric cancer and triple-negative breast cancer [ 79 , 80 , 81 ], FGFR1 chromosomal translocation occurs at the 8p11 locus in myelodysplastic syndrome and alveolar rhabdomyosarcoma [ 82 ], FGFR3 chromosomal translocation occurs in multiple myeloma and peripheral T-cell lymphoma [ 83 , 84 ], missense mutations in the FGFR2 gene are found in endometrial cancer and melanoma [ 85 , 86 ], mutations in the FGFR3 gene result in invasive bladder cancer [ 87 , 88 ], and the FGFR4 mutation is correlated with Rhabdomyosarcoma [ 89 , 90 ].…”

Section: Drug Development and Clinical Application Of Fgf Familymentioning

confidence: 99%

FGF Family: From Drug Development to Clinical Application

Jin

et al. 2018

IJMS

135

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Fibroblast growth factor (FGF) belongs to a large family of growth factors. FGFs use paracrine or endocrine signaling to mediate a myriad of biological and pathophysiological process, including angiogenesis, wound healing, embryonic development, and metabolism regulation. FGF drugs for the treatment of burn and ulcer wounds are now available. The recent discovery of the crucial roles of the endocrine-acting FGF19 subfamily in maintaining homeostasis of bile acid, glucose, and phosphate further extended the activity profile of this family. Here, the applications of recombinant FGFs for the treatment of wounds, diabetes, hypophosphatemia, the development of FGF receptor inhibitors as anti-neoplastic drugs, and the achievements of basic research and applications of FGFs in China are reviewed.

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Targeting fibroblast growth factor receptor (FGFR) pathway in renal cell carcinoma

Cited by 22 publications

References 32 publications

Gene expression-based biomarkers for discriminating early and late stage of clear cell renal cancer

Gene expression-based biomarkers for discriminating early and late stage of clear cell renal cancer

Inhibition of FGF2-Mediated Signaling in GIST—Promising Approach for Overcoming Resistance to Imatinib

FGF Family: From Drug Development to Clinical Application

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