Clofarabine in bladder cancer

Bladder cancer is amongst the most frequent cancer types worldwide and requires intense, long-term therapy. Patients with bladder cancer rarely benefit from chemotherapy. This is especially relevant for patients diagnosed with aggressive or metastatic tumors. Therefore, there is a strong need for more efficient therapeutic options. Our lab has recently described potent bladder cancer-killing activity of the substance clofarabine. This substance is already in clinical use to treat other tumor types, which makes it attractive for rapid applicability as treatment also for patients with bladder cancer. However, to this end, additional experiments will be necessary to describe the molecular mechanisms that determine sensitivity and resistance of bladder cancer cells towards clofarabine. We have therefore generated a large collection of cell models from human bladder tumors. These cancer cell cultures are well suited to investigate new therapeutic approaches such as using clofarabine. One important factor to do so successfully lies in the necessity to choose cell models that are as similar as possible to human tumors. For this reason, we will characterize our models thoroughly at the molecular level (e.g., identifying changes in their genetic code). This scientifically interesting collection will be a valuable resource for our lab, but also for the broader bladder cancer research community, because it will enable us to elaborate new therapeutic concepts. In the most suitable models, we will investigate factors that determine the cell-killing potential, but also resistance mechanisms of clofarabine, using the so-called single-cell RNA sequencing technology. This will be followed by computer science-assisted analyses and experiments in cell culture and corresponding patient material. In doing so, we hope to identify molecular targets which we can additionally exploit therapeutically in order to reduce the risk of therapy resistance development and increase the tumor-killing potential of clofarabine.