Richard Koche

The support from the Stiftung Charité Foundation for this BIH Visiting Professorship served to stimulate novel research in pediatric oncology as well as solidify a long-term relationship between scientists at Memorial Sloan Kettering Cancer Center and the Charité – Universitätsmedizin Berlin. The overlapping research interests and complementary skillsets of physician-scientists and computational biologists allow for the kinds of synergy required of an era when data is easier to generate but real solutions to pressing problems in cancer biology are not easily discovered. This collaboration not only helped train bench and physician-scientists in data interpretation and analysis, but also opened up a new lines of inquiry for the development and potential treatment of pediatric cancers.
Extrachromosomal circular DNA (ecDNA) is a previously underappreciated oncogenic driver in as many as 30% of all cancers over time, and a likely culprit behind tumor heterogeneity and therapy resistance. Our studies focused on neuroblastoma, the most common extracranial solid tumor of childhood, and one in which ~25% of patients have ecDNA-driven tumors. Through work under the leadership of Prof. Dr. Angelika Eggert and conducted in the laboratory of Prof. Dr. Anton Henssen, we sought to better understand the role of circular DNA in neuroblastoma tumorigenesis. We employed a variety of computational and experimental approaches to focus on three key areas: i) enhanced detection and classification of circular DNA, ii) the functional consequences of circular DNA on both the circulome as well as linear chromosomes, and iii) implications for the clinical trajectory of neuroblastoma patients. Discoveries made in all three areas through the course of this Visiting Professorship have led to publications in high-impact journals as well as awards recognizing our innovative approaches to difficult problems in cancer biology. These collaborative studies on ecDNA provide fertile ground from which numerous future studies can be launched, and, importantly, lend insight into tumor evolution and therapy resistance, potentially opening new avenues of exploration for novel therapeutics for a pediatric tumor with no viable treatment options.