Tackling FGFR3-driven bladder cancer with a promising synergistic FGFR/HDAC targeted therapy.
Tackling FGFR3-driven bladder cancer with a promising synergistic FGFR/HDAC targeted therapy.
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DOI：
10.1038/s41698-023-00417-5
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发表时间：
2023-07-21
影响因子：
7.9
通讯作者：
中科院分区：
文献类型：
--
作者：
Bladder cancer (BC) is one of the most prevalent malignancies worldwide and FGFR3 alterations are particularly common in BC. Despite approval of erdafitinib, durable responses for FGFR inhibitors are still uncommon and most patients relapse to metastatic disease. Given the necessity to discover more efficient therapies for BC, herein, we sought to explore promising synergistic combinations for BC with FGFR3 fusions. Our studies confirmed the synergy between FGFR and HDAC inhibitors in vitro and demonstrated its benefits in vivo. Mechanistic studies revealed that quisinostat can downregulate FGFR3 expression by suppressing FGFR3 translation. Additionally, quisinostat can also sensitize BC cells to erdafitinib by downregulating HDGF. Furthermore, the synergy was also confirmed in BC cells with FGFR3 S249C. This study discovers a new avenue for treatment of FGFR3-driven BC and uncovers new mechanistic insights. These preclinical studies pave the way for a direct translation of this combination to early phase clinical trials.
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影响因子：
11.1
作者：
Mahe M;Dufour F;Neyret-Kahn H;Moreno-Vega A;Beraud C;Shi M;Hamaidi I;Sanchez-Quiles V;Krucker C;Dorland-Galliot M;Chapeaublanc E;Nicolle R;Lang H;Pouponnot C;Massfelder T;Radvanyi F;Bernard-Pierrot I
通讯作者：
Bernard-Pierrot I
影响因子：
11.5
作者：
Arts, Janine;King, Peter;Angibaud, Patrick
通讯作者：
Angibaud, Patrick
DOI：
10.1002/path.5143
发表时间：
2018-11
期刊：
The Journal of pathology
影响因子：
--
作者：
Foth M;Ismail NFB;Kung JSC;Tomlinson D;Knowles MA;Eriksson P;Sjödahl G;Salmond JM;Sansom OJ;Iwata T
通讯作者：
Iwata T
影响因子：
3.7
作者：
Mithraprabhu, Sridurga;Kalff, Anna;Spencer, Andrew
通讯作者：
Spencer, Andrew
影响因子：
5.7
作者：
Gust KM;McConkey DJ;Awrey S;Hegarty PK;Qing J;Bondaruk J;Ashkenazi A;Czerniak B;Dinney CP;Black PC
通讯作者：
Black PC