Different stages in drug development for muscle-invasive bladder cancer

Abstract

Muscle-invasive bladder cancer (MIBC) is a highly aggressive disease. Despite optimal therapy, half of the patients will succumb to disease. This prognosis could not be improved over the last three decades. Therefore, MIBC is left behind from other cancers such as prostate, where novel treatment options were discovered and improve patient outcomes. While being aware of the recent emerging evidence of checkpoint inhibition in MIBC, we aim to describe different stages of drug development in MIBC by using three specific targets. On the example of Her2 targeting, we aimed to indicate, that either a target is ineffective in MIBC or that the patient selection is insufficient. The first clinical trials using a pan fibroblast growth factor receptor (panFGFR) inhibitor to target the FGFR pathway showed promising results. Data of further trials are to be awaited before implementing these drugs into daily clinical practice. A large variety of novel agents are investigated in vitro and in vivo. On the example of a malaria protein, we aimed to discuss a treatment paradigm that is not dependent on pathway signaling and the genomic landscape of MIBC. The ultimate question still remains to be answered: How do we select the optimal treatment for the right patient?

Keywords: Bladder cancer; drug development; patient selection; targeted therapies.