fosciclopirox + gemcitabine + cisplatin

This is a **combination chemotherapy regimen** for muscle invasive and non-muscle invasive bladder cancer that includes **fosciclopirox (CPX-POM)**, **gemcitabine**, and **cisplatin**. Fosciclopirox is a phosphoryloxymethyl ester prodrug of ciclopirox, originally developed as an antifungal, but repurposed for oncology as an injectable small molecule. Once administered, it is rapidly metabolized to ciclopirox, which inhibits the **γ-secretase complex** (Presenilin 1, Nicastrin), suppressing Notch and Wnt signaling pathways implicated in tumor progression and maintenance[4][6]. Gemcitabine is a nucleoside analog that inhibits DNA synthesis by blocking DNA polymerase and ribonucleotide reductase. Cisplatin is a platinum-based compound that causes DNA crosslinking, leading to apoptosis of cancer cells[1][2][3][5]. The triple combination is under investigation in clinical trials in **bladder cancer**, with fosciclopirox added to standard gemcitabine + cisplatin (which is broadly used for biliary tract cancer, bladder cancer, cervical cancer, malignant mesothelioma, non-small cell lung cancer, ovarian cancer, and pancreatic cancer)[1][4]. Early clinical proof-of-concept shows good tolerability, evidence of target inhibition, and possible increased efficacy compared to standard doublet therapy[4].

Other names

CPX-POM + gemcitabine + cisplatin