SYMPATHY

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.

Publications

Roider, T., J. Seufert, A. Uvarovskii, F. Frauhammer, M. Bordas, N. Abedpour, M. Stolarczyk, J.-P. Mallm, S. A. Herbst, P.-M. Bruch, H. Balke-Want, M. Hundemer, K. Rippe, B. Goeppert, M. Seiffert, B. Brors, G. Mechtersheimer, T. Zenz, M. Peifer, B. Chapuy, M. Schlesner, C. Müller-Tidow, S. Fröhling, W. Huber, S. Anders and S. Dietrich (2020). "Dissecting intratumour heterogeneity of nodal B-cell lymphomas at the transcriptional, genetic and drug-response levels." Nat Cell Biol: 1–11. doi.org/10.1038/s41556-020-0532-x.

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. and Zenz, T. (2018). "Drug-perturbation-based stratification of blood cancer." The Journal of Clinical Investigation 128(1): 427-445. www.ncbi.nlm.nih.gov/pubmed/29227286.

Liebers, N., Roider, T., Bohn, J. P., Haberbosch, I., Pircher, A., Ferstl, B., Ebnother, M., Wendtner, C. M., Dearden, C., Follows, G. A., Ho, A. D., Muller-Tidow, C., Dreger, P., Troussard, X., Zenz, T. and Dietrich, S. (2019). "BRAF inhibitor treatment in classic hairy cell leukemia: a long-term follow-up study of patients treated outside clinical trials." Leukemia. www.ncbi.nlm.nih.gov/pubmed/31740808.