Treatment response in cancer is influenced by multiple biological factors including genetic alterations of tumor cells and the tumor microenvironment. While many of these factors can be characterized in tumor biopsies and used for diagnosis, treatment stratification and prediction of prognosis, the interplay and direct effects on drug response are often incompletely understood.

To investigate modulators of therapy response in patients, we can model drug response ex vivo. For this, we isolate primary tumor cells from peripheral blood or diagnostic biopsies and treat them with a large library of clinically available and experimental drugs.

This Drug Response Profiling (DRP) has helped us understand genetic modulators of drug response (Dietrich et al. 2012; Dietrich et al. 2018; Janssen et al. 2022), uncovered the microenvironmental impact on drug response (Herbst et al. 2022; Bruch et al. 2022) and identified mechanisms of drug resistance (Roider et al. 2020; Lu et al. 2021).

Additionally to important biological findings, ex vivo DRP can be used to predict the response of individual patients beyond known markers of therapy resistance. We previously performed the non-interventional prospective SMARTrial in which we directly correlated in vivo treatment response of patients with hematologic malignancies to ex vivo DRP. Based on this readout, we were able to treat patients who lacked any further standard treatment options. In one such case, we identified a surprising sensitivity to folate inhibitors which showed great clinical efficacy and enabled a subsequent allogeneic stem cell transplantation. (Liebers et al. 2019) This particular patient remains free of relapse multiple years after the stem cell transplantation.

Thereby, ex vivo DRP profiling has the potential to optimize treatment selection for cancer patients and in individual cases opens up new treatment options when standard-of-care treatment has failed.

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