The resistance to cell death is one of the hallmarks of cancer. This means that in order for a tumour to grow, cancer cells need to evolve to survive and ignore death-inducing signals coming from the environment. This also implies that the induction of apoptosis is really important for cancer therapy to work and fully eliminate tumours. In our lab we are studying the deregulation of apoptosis in cancer and aim to identify novel ways to activate apoptosis in cancer cells. The projects described below explain how we study apoptosis in cancer cells in our lab:
Neuroblastoma
Discovering novel ways to overcome resistance to conventional therapy
In this project we are investigating how apoptosis can be restarted after failure of conventional chemotherapy. To this end we use chemoresistant neuroblastoma cells derived from the Resistant Cancer Cell Line collection to study how apoptotic signalling is altered during chemoresistance. Thereby, we hypothesize that deregulation of the BCL2 proteins is a fundamenal way to acquire drug resistance, and that hence treatment with BH3 mimetics may be a possible treatment option to combat chemoresistance.
Cellular immune therapy
Although the survival of children with cancer has improved, the high-risk patient groups still have low overall survival and need better treatment options. In our lab we investigate how immune therapy based on Natural Killer (NK) cells can be applied to induce apoptosis in solid tumours like Rhabdomyosarcoma. In the video displayed on the left we show how we layer blood on top of the clear Ficoll fluid to isolate the immune cells.
Lymphoma
Understanding mechanisms of BH3 mimetic induced apoptosis in Diffuse Large B-cell Lymphoma
BH3 mimetics are highly promising novel therapeutics for the treatement of leukemia. In this project, we aim to understand why lymphoma cells are more resistant to BH3 mimetics and identify ways to apply BH3 mimetics also in lymphoma.
Establishing novel models for pediatric cancer
In order to more faithfully recapitulate the complex tumour environment in a cancer patient we are currently establishing novel models to study pediatric cancer. In collaboration with Elise Gradhand and her team at the Senckenberg Institute for Pathology we obtain tumour tissue for processing and culture in the lab. The derived primary cells can grow in 3D tumour spheroids and allow drug testing in the lab.
