UM Data Science Research Seminar
The UM Data Science Research Seminar Series are monthly sessions organised by the Institute of Data Science, on behalf of the UM Data Science Community, in collaboration with different departments across UM with the aim to bring together data scientists from Maastricht University to discuss breakthroughs and research topics related to Data Science.
This session is organised in collaboration with Precision Medicine on 18 June 2020, from 12.00 - 13.00 hrs.
12.00 - 13.00
Talk by Alexander van der Wiel and Saeed Masroor
Title: Identification of key factors contributing to the antitumor effects of the hypoxia-activated prodrug CP-506: a modeling approach
Abstract: Hypoxia-activated prodrugs (HAPs) are a promising class of antineoplastic agents that selectively target hypoxic tumor cells associated with malignancy and treatment resistance. However, the majority of HAP clinical trials yielded disappointing results, with a lack of patient stratification at least in part accountable for their failure. As gaining mechanistic understanding is crucial for successful clinical implementation, the present study employed a modeling approach to identify key factors contributing to the antitumor effects of the novel HAP CP-506. As hypoxia is one of these proposed key factors, a first and necessary step in fully capturing its effects on the efficacy of CP-506 is appreciating the oxygen distribution in tumors. In order to do so, we used mathematical modeling of oxygen diffusion and consumption at a micrometer scale of in vitro 3D spheroid cell cultures. Next, to identify which factors can predict the in vivo treatment outcome of CP-506, we developed and validated a logistic regression model using an extensive dataset comprised of more than 350 animals. In this presentation, we will introduce the principles of HAPs and the basics of the modeling approaches used, as well as their potential applications in improving cancer therapy outcome.