Abstract

Modeling Heterogenous Responses to DNA-Damaging Cancer Drugs

Bart Westendorp, Assistant Professor, Department of Pathobiology, Utrecht University The Netherlands

Unraveling mechanisms of acquired drug resistance in solid cancers is a major goal to improve the prognosis of cancer patients. An important concept in cancer drug resistance is the presence of (rare) drug-tolerant persister cells, which manage to withstand the effect of cancer medication by modifying their gene expression program, metabolism, and proliferation speed. But the cell-autonomous and environmental factors that determine whether -and how frequently- such persister cells emerge are still poorly understood. In addition, molecular events eventually triggering the emergence of fully drug-resistant relapsed tumors are enigmatic. I will show how we study tolerance and resistance to targeted inhibitors of DNA damage responses in bladder and ovarian cancer. One major challenge is the difficulty to study drug-tolerant persister cells in vivo. I will discuss the possibilities and opportunities for tumor spheroid models in this research field.