Intercept clonal evolution to overcome treatment resistance in childhood and adult blood cancer
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 channel relapsing blood cancer patients in Zurich into a new Innovation Clinic (see figure 5). 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 to drugs of these collected tumor samples, at multiple levels of their molecular biology and at single-cell resolution. This will enable us to understand the heterogeneity of tumor and normal immune cells and their interactions. The screens 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%.