Systems medicine approach to establish individualized treatment of lymphoma and leukemia
We aim to establish a systems medicine program that integrates systematic functional assays, multi-omic profiling, bioinformatic analysis, mathematical modeling and setup towards a clinical exploitation. The basis of the program is a platform to map patient specific pathway activity and drug sensitivity of their primary tumor cells ex- vivo. Signals provided by the microenvironment modify pathway activities, including those targeted by drugs, and thereby can mediate resistance or sensitivity to these drugs. We generate a systems-level understanding of how the microenvironment and the individual genetic and molecular make-up of a tumor interact and modify drug response using a high throughput automated microscopy platform mimicking microenvironment conditions. By comparing drug responses across patients with detailed molecular characterization and the clinical parameters, we obtain a rich set of associations of drug sensitivity with biology, biomarkers and outcome. The long-term aim of this work is to bring biology-based individualized treatment of lymphoma and leukemia into clinical practice.
Dietrich, S., Oleś, M., Lu, J., Sellner, L., Anders, S., Velten, B., Wu, B., Hüllein, J., da Silva Liberio, M., Walther, T., Wagner, L., Rabe, S., Ghidelli-Disse, S., Bantscheff, M., Oleś, A.K., Słabicki, M., Mock, A., Oakes, C.C., Wang, S., Oppermann, S., Lukas, M., Kim, V., Sill, M., Benner, A., Jauch, A., Sutton, L.A., Young, E., Rosenquist, R., Liu, X., Jethwa, A., Lee, K.S., Lewis, J., Putzker, K., Lutz, C., Rossi, D., Mokhir, A., Oellerich, T., Zirlik, K., Herling, M., Nguyen-Khac, F., Plass, C., Andersson, E., Mustjoki, S., von Kalle, C., Ho, A.D., Hensel, M., Dürig, J., Ringshausen, I., Zapatka, M., Huber, W., Zenz, T., 2018. Drug-perturbation-based stratification of blood cancer. J. Clin. Invest. 128, 427–445. doi.org/10.1172/JCI93801