New Precision Medicine Initiative funded through LOOP (Link - Home - The LOOP Zurich)

INTeRCePT: Intercept clonal evolution to overcome treatment resistance in childhood and adult blood cancer

Person repsonsible: Thorsten Zenz (USZ/UZH), Burkhard Becher (UZH), Nico Beerenwinkel (ETHZ), Jean-Pierre Bourquin (KISPI/UZH), Wolfgang Huber (EMBL), Andreas Moor (ETHZ), Berend Snijder (ETHZ)

Summary: Patients with lymphoma or acute lymphoblastic leukemia who do not respond to treatment have a bleak outcome. Over 1100 patients die with leukemia and lymphoma in Switzerland annually, despite a diverse treatment landscape. There is a major need to optimize treatment selection for patients with blood cancer.

To improve the outcome of lymphoid malignancies in children and adults, we will channel relapsing blood cancer patients in Zurich into a new Innovation Clinic. Treatments are applied, often multiple times consecutively, and each time tumors and normal blood cells are collected before treatment. In laboratory experiments, we determine the precise molecular state as well as the dynamic response of these collected tumor samples, at multiple levels of their molecular biology and at single-cell resolution. This will also enable us to understand the heterogeneity of tumor and normal immune cells and their interactions. The drugs will include all drugs potentially available for treatment, including those used in the patient. By computational analysis, we construct a detailed single-cell map of drug response and use this to derive a broadly applicable procedure aimed at extinction of the tumor (INTeRCePT), which we test in a trial, aiming to increase response rate by 50%.