The Vogler lab develops new strategies to fight chemotherapy-resistant neuroblastoma

Neuroblastoma is an aggressive neuronal tumor that occurs mostly in infants and children under the age of six. The common therapy for neuroblastoma is based on intensive chemotherapies in addition to surgical resection. A frequently occurring problem in neuroblastoma consists in the relapse of aggressive, treatment-resistant tumors after chemotherapy. Improved therapies and novel treatment strategies for these patients are therefore urgently required. In this research project – funded by the Madeleine Schickedanz Children’s Cancer Foundation and German Cancer Aid – performed at the Institute of Experimental Pediatric Hematology and Oncology, the Vogler lab focused on the goal to overcome therapy resistance by in-depth mechanistic analyses of programmed cell death (apoptosis) in treatment-resistant neuroblastoma cells. The induction of apoptosis is regulated primarily by the BCL2 protein family. Therefore, the inhibition of BCL2 proteins represents a new approach in cancer research that can specifically induce cancer cell death. This new approach benefits from the availability of approved drugs for BCL2 inhibition and a plethora of ongoing clinical trials for additional members of the BCL2 protein family (so-called BH3 mimetics). To understand how BCL2 protein function changes in chemotherapy-resistant cells, in collaboration with Professor Cinatl (IDL) the scientists of the Vogler lab leveraged chemotherapy-resistant neuroblastoma cells to show how the dependency on individual members of the BCL2 protein family is shifting in chemotherapy-resistant cells. As a result, chemoresistance generates new targets for selective BH3 mimetics. This study has recently been published in the prestigious journal British Journal of Cancer and is publicly available here (www.nature.com). The findings obtained by the Vogler lab in this study are an important step towards the use of apoptosis-inducing therapeutics such as BH3 mimetics and underline the importance of molecular cancer research for the further development of therapeutic options for children with cancer.