Targeting FGFR pathway in breast cancer

Peréz-García, José Manuel; Muñoz‐Couselo, Eva; Soberino, Jesús; Racca, Fabricio; Cortés, Javier

doi:10.1016/j.breast.2017.10.014

Cited by 103 publications

(93 citation statements)

References 47 publications

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“…FGFR overexpression thus does not appear to result from FGFR amplification and might be the result of posttranscriptional or posttranslational regulation mechanisms. Note that FGFR overexpression without FGFR gene amplification has been described in other tumor types [ 38 ] and [ 40 ].…”

Section: Discussionmentioning

confidence: 98%

“…Our findings therefore suggest that FGFR1 and FGFR4 expression may serve as predictive biomarkers allowing the stratification of patients for inclusion in FGFR inhibitor clinical trials. Several publications have discussed the important issue of FGFR amplification value versus mRNA and protein expression as biomarkers to predict efficacy of FGFR inhibitors [ 38 ]. FGFR amplification appears to be a rare event in WDLPS and DDLPS.…”

Section: Discussionmentioning

confidence: 99%

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Novel Therapeutic Insights in Dedifferentiated Liposarcoma: A Role for FGFR and MDM2 Dual Targeting

Dadone‐Montaudie

Laroche-Clary

Mongis

et al. 2020

Cancers

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We aimed to evaluate the therapeutic potential of the pan-FGFR inhibitor erdafitinib to treat dedifferentiated liposarcoma (DDLPS). FGFR expression and their prognostic value were assessed in a series of 694 samples of well-differentiated/dedifferentiated liposarcoma (WDLPS/DDLPS). The effect of erdafitinib—alone or in combination with other antagonists—on tumorigenicity was evaluated in vitro and in vivo. We detected overexpression of FGFR1 and/or FGFR4 in a subset of WDLPS and DDLPS and demonstrated correlation of this expression with poor prognosis. Erdafitinib treatment reduced cell viability, inducing apoptosis and strong inhibition of the ERK1/2 pathway. Combining erdafitinib with the MDM2 antagonist RG7388 exerted a synergistic effect on viability, apoptosis, and clonogenicity in one WDLPS and two DDLPS cell lines. Efficacy of this combination was confirmed in vivo on a DDLPS xenograft. Importantly, we report the efficacy of erdafitinib in one patient with refractory DDLPS showing disease stabilization for 12 weeks. We provide evidence that the FGFR pathway has therapeutic potential for a subset of DDLPS and that an FGFR1/FGFR4 expression might constitute a powerful biomarker to select patients for FGFR inhibitor clinical trials. In addition, we show that combining erdafitinib with RG7388 is a promising strategy for patients with DDLPS that deserves further investigation in the clinical setting.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Novel Therapeutic Insights in Dedifferentiated Liposarcoma: A Role for FGFR and MDM2 Dual Targeting

Dadone‐Montaudie

Laroche-Clary

Mongis

et al. 2020

Cancers

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“…It has been demonstrated that tumorigenesis will be withdrawn if the signal pathways of tumor angiogenesis are blockaded [4]. Thus, angiogenesis inhibition may be a viable treatment approach for the highly vascular tumor types, such as ovarian cancer, lung cancer and breast cancer [5][6][7]. However, targeting single factor may produce drug resistance and compensatory angiogenesis because the roles of other factors may be strengthened [8].…”

Section: Introductionmentioning

confidence: 99%

Large‐scale production, purification, and function of a tumor multi‐epitope vaccine: Peptibody with bFGF/VEGFA

Zhang

Jiang

Chen

et al. 2020

Engineering in Life Sciences

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In tumor tissue, basic fibroblast growth factor (bFGF) and vascular endothelial growth factor A (VEGFA) promote tumorigenesis by activating angiogenesis, but targeting single factor may produce drug resistance and compensatory angiogenesis. The Peptibody with bFGF/VEGFA was designed to simultaneously blockade these two factors. We were aiming to produce this Fc fusion protein in a large scale. The biological characterizations of Peptibody strains were identified as Escherichia coli and the fermentation mode was optimized in the shake flasks and 10‐L bioreactor. The fermentation was scaled up to 100 L, with wet cell weight (WCW) 126 g/L, production 1.41 g/L, and productivity 0.35 g/(L·h) of IPTG induction. The target protein was isolated by cation‐exchange, hydrophobic and Protein A chromatography, with total recovery of 60.28% and HPLC purity of 86.71%. The host cells protein, DNA, and endotoxin residues were within the threshold. In mouse model, immunization of Peptibody vaccine could significantly suppressed the tumor growth and angiogenesis, with inhibition rate of 57.73 and 39.34%. The Peptibody vaccine could elicit high‐titer anti‐bFGF and anti‐VEGFA antibodies, which inhibited the proliferation and migration of Lewis lung cancer cell cells by decreasing the Akt/MAPK signal pathways. Therefore, the Peptibody with bFGF/VEGFA might be used as a therapeutic tumor vaccine. The large‐scale process we developed could support its industrial production and pre‐clinical study in the future.

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“…CTKI258A2210), but the efficacy of this combination was minimal, even in patients pre-selected for alterations in the FGFR pathway. 31 A potential underlying explanation for this lack of benefit is that FGFR alterations impinge upon downstream signaling networks shared by many other receptor tyrosine kinases. Figure 4 shows CDGnet recommendations for a breast cancer patient with overexpression of both ESR1 (gene encoding ER) and FGFR1, when considering only FDAapproved targeted therapies.…”

Section: Resultsmentioning

confidence: 99%

An evidence-based network approach to recommending targeted cancer therapies

Kancherla

Rao

Bhuvaneshwar

et al. 2019

Preprint

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In this work, we introduce CDGnet, an evidence-based network approach for recommending targeted cancer therapies, available as a user-friendly informatics tool. Our approach can be used to expand the range of options of targeted therapies for cancer patients who undergo molecular profiling. It considers biological pathway information specifically by looking at downstream targets of oncogenes and is personalized for individual patients via the user-inputted molecular alterations and cancer type. CDGnet integrates disparate sources of knowledge and provides results in a number of easily-accessible and usable forms, while separating targeted cancer therapies into categories in an evidence-based manner.

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Targeting FGFR pathway in breast cancer

Cited by 103 publications

References 47 publications

Novel Therapeutic Insights in Dedifferentiated Liposarcoma: A Role for FGFR and MDM2 Dual Targeting

Novel Therapeutic Insights in Dedifferentiated Liposarcoma: A Role for FGFR and MDM2 Dual Targeting

Large‐scale production, purification, and function of a tumor multi‐epitope vaccine: Peptibody with bFGF/VEGFA

An evidence-based network approach to recommending targeted cancer therapies

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