We at the Systems Biology for Oncology Group use a combined computational and experimental approach to unravel the intricate mechanism shaping the tumor microenvironment. We use mathematical models based on clinical data and cancer biology to identify factors influencing individual response to therapy with the ultimate aim of improving precision oncology. Given the heterogeneous and dynamic nature of tumor response to therapy, perturbation biology has shown the potential to overcome the limitation of genomic biomarkers.
Our approach involves subjecting receptive tumor cells to an extensive anti-cancer drug screen to identify phenotypic properties of tumors in order to determine more effective anti-cancer treatments. Microfluidics is a valuable technology which aids in the analysis of a small amount of sample such as tumor biopsy by distributing it into individual compartments such as droplets or plugs. It also allows in the control of the composition of each plug, thereby creating multiple populations of chemically distinct plugs.
We present here a fully PDMS based device where fluid flow is regulated by pressure actuated quake valves, which allow for the quick, controlled, and programmable production of distinct plug populations. Furthermore, since the quake valves are also PDMS based, they can be integrated smoothly into device fabrication. Combining data obtained from eye throughput combinatorial screening of cancer cells with mathematical models will allow us to study signaling pathways regulating the tumor microenvironment behavior.
This research will pave the way for new strategies for precision oncology providing the rationale to personalize treatment to individual patients.
