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Ref Type Journal Article
PMID (37479885)
Authors Wang Z, Muthusamy V, Petrylak DP, Anderson KS
Title Tackling FGFR3-driven bladder cancer with a promising synergistic FGFR/HDAC targeted therapy.
Journal Vol Issue Date Pages Journal Short Title
NPJ precision oncology 7 1 2023 Jul 21 70 NPJ Precis Oncol
URL
Abstract Text 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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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
FGFR3 S249C urinary bladder cancer sensitive Erdafitinib + Quisinostat Preclinical - Cell culture Actionable In a preclinical study, the combination of Balversa (erdafitinib) and Quisinostat (JNJ-26481585) synergistically inhibited viability in a bladder cancer cell line harboring FGFR3 S249C in culture (PMID: 37479885). 37479885