Investigational cell cycle inhibitors in clinical trials for bladder cancer

Cancer-related cell cycle defects are often mediated by alterations in activity of diverse cell cycle regulators. The development of cell cycle inhibitors has undergone a gradual evolution, and new investigational drugs have been extensively tested as a single agent or combination with conventional chemotherapeutic drugs.

This review covers a broad perspective of how the cell cycle is deregulated in bladder cancer and discusses the clinical trials of cell cycle inhibitors.

Although diverse cell cycle inhibitors have been considered as relevant drug candidates for cancer therapy owing to their potential role in restoring control of the cell cycle, these inhibitors have not been yet widely tested in human bladder cancer. Numerous studies already reported that deregulation of cell cycle controls has been commonly observed in bladder cancer cells, thus warranting clinical trials of these inhibitors in advanced bladder cancer patients. In addition, nonmuscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC) show different clinical and molecular biological characteristics, although ∼ 10 - 20% of NMIBC will progress to MIBC. Therefore, adequate cell cycle inhibitors have to be chosen for bladder cancer treatment based on the different genetic features between NMIBC and MIBC related to cell cycle regulators.