Investigation of the molecular mechanisms of the synergy between erdafitinib and quisinostat

We first verified that erdafitinib is synergistic with quisinostat in vitro and confirmed that the combinational treatment can significantly enhance the inhibition of tumor growth and prolong the survival in vivo for bladder cancers with FGFR3 fusions. Next, in order to understand the underlying molecular mechanisms of this synergy, we performed RNA-seq analysis. We revealed that quisinostat can concomitantly inhibit FGFR signaling with erdafitinib by suppressing the translation of FGFR3 fusions. In addition, quisinostat can also sensitize bladder cancer cells to erdafitinib by downregulating HDGF, which is a second mechanism of the synergy independent of FGFR signaling. We have three bladder cancer cell lines with FGFR3 fusions: RT4, RT112, and SW780. We treated all three cells with quisinostat or DMSO control. And then we extracted mRNA and performed RNA-seq analysis.