Pediatric Cancer Metabolism
The Morscher Lab focuses on understanding the reprogramming of metabolism across pediatric cancer types. We are interested in both, understanding fundamental principles of cancer biology and translational research developing novel metabolism targeting treatment strategies for children with cancer.
Two major challenges treating children with cancer
- More than half of the children with relapsed refractory cancers die from their disease. In this high risk population novel therapies are urgently needed.
- When cured from cancer, childhood cancer survivors go on to live for decades of years. We therefore need to develop low toxicity therapy regimens to replace genotoxic chemotherapies.
In our group we address both of these challenges. Targeting metabolism not only offers promising new therapy targets, but also non-genotoxic approaches with limited long-term effects on the child’s body.
Metabolism is a complex network of small molecules (metabolites) and proteins (enzymes). By providing energy and building blocks this network is key for cell survival and growth. In order to proliferate cancer cells have specific needs that make them vulnerable for novel therapies. In our group we leverage recent advances in technology to understand the specific metabolic requirements of cancers in children. Our ultimate goal is to develop novel therapies that cure children. Therefore, we have a team of basic scientists and clinicians working closely together to advance findings to clinical translation.
Cancers in children are different from adults. They harbor less mutations and the cause of cancer development is often linked to defined genetic drivers. This project focuses on understanding the principles of metabolic reprogramming across different pediatric cancer types. We use this approach to reveal cancer type specific metabolic dependencies and vulnerabilities.
Whole genome and RNA-Sequencing of cancers has led to profound understanding of the genetic landscape of cancers. Most work has been focusing on known regulators of cell growth and cell fate. In this project, we aim to leverage existing data from one of the world’s largest precision medicine trial in children (MAPPYACTS) to find patient specific genetic changes in metabolic pathways and genes in order to match them to individual treatments. This work is done in collaboration with Prof. Dr. Birgit Geoerger at Institut Gustave Roussy.
Our ultimate goal is to provide novel treatment options to children with cancer. After identifying novel targets they are either linked to existing drugs or novel compounds need to be developed. We therefore closely work together with groups focusing on new drug development such as Dr. Catherine Brenner at Université Paris-Saclay.
In many pediatric cancers activity the transcription factor MYC is upregulated. This protein has been shown to be a master regulator of cellular metabolism. We use cell culture and in-vivo models to understand its role in pediatric cancers and how this can be used to develop novel therapy approaches. Together with our partners at the Children’s Hospital of Philadelphia (Dr. Michael Hogarty) and Princeton (Prof. Rabinowitz) we are currently specially focusing on its role in amino acid metabolism.
Zwei grosse Herausforderungen bei der Behandlung krebskranker Kinder
- Mehr als die Hälfte der Kinder mit wiederkehrenden oder therapieresistenten Krebserkrankungen stirbt an ihrer Krankheit. Für diese Hochrisikogruppe werden dringend neue Therapien benötigt.
- Wenn Kinder von Krebs geheilt werden, leben sie noch Jahrzehnte weiter. Wir müssen daher Therapien mit geringer Toxizität entwickeln, um Langzeitfolgeschäden zu verhindern.
In unserer Gruppe befassen wir uns mit diesen beiden Herausforderungen. Die Ausrichtung auf den Stoffwechsel bietet nicht nur vielversprechende neue Therapieziele, sondern auch nicht-genotoxische Ansätze mit begrenzten langfristigen Auswirkungen auf den Körper des Kindes.