Chronic lymphocytic leukemia
Chronic lymphocytic leukemia (CLL) is the most common leukemia in western countries, typically occurring in elderly patients. It has a variable, but usually slowly progressive, clinical course. New drugs were approved for the treatment of CLL, such as Ibrutinib, Idelalisib and Venetoclax. However, no biomarkers have been identified to guide the choice of treatment for each patient in particular, leading to selection of treatments based on the drugs’ toxicity profile and patients’ comorbidities rather than tumor sensitivity. Often the patient is treated with some of these expensive drugs in sequence, being exposed to unnecessary toxicity with no beneficial results. Pre-testing tumor cells’ sensitivity to the available drugs would allow for tailored therapy, avoiding unnecessary toxicities and costs with a significant impact on the patients’ quality of life and healthcare systems.
Our collaborator, Fior and colleagues, developed zebrafish patient-derived xenografts (zPDX) to screen therapeutics for cancer (Fior et al, 2017). In this project, we are exploring the same model to determine in vivo differential sensitivity of patient-derived CLL cells to novel drugs available. We will compare patient response to treatment to their matching zPDX and in this way test the predictability of the model. If this project proves successful, we will have developed a new in vivo screening platform for CLL.