Investigating the Origins of Neuroblastoma and Nephroblastoma

(Vienna, 15.02.2024) The cellular changes leading to the development of cancer in children are still largely unknown, especially in the case of embryonal tumors. A new study led by Florian Halbritter, Principal Investigator at St. Anna Children’s Cancer Research Institute (St. Anna CCRI), aims to elucidate why certain genetic mutations are more likely to yield tumors of specific developmental lineages than of others. This research project is supported by the Austrian Science Fund (FWF).

Cancer remains one of the most common causes of death in children, despite the increasing knowledge of mutations causing cancer and improvements in therapy. One contributing factor is that the origins of many types of tumors are still largely unclear. A team led by Florian Halbritter, Principal Investigator at St. Anna Children’s Cancer Research Institute, now seeks to explore why not all cells with genetic mutations develop into tumors, focusing on one kidney tumor (nephroblastoma) and one nerve tumor (neuroblastoma) as an example.

Both kidney tumors and nerve tumors develop in children during embryonic stages and are developmentally closely related, although they originate from different tissues that may share the same genetic mutations. “Just because the same mutations exist in both tissues does not necessarily mean that both tissues will develop tumors,” explains Halbritter. The researcher aims to uncover the reasons for this phenomenon in the study funded by the Austrian Science Fund (FWF).

Stem Cell Models for Origin Analysis

To this end, the researcher reconstructs the developmental pathways of the kidney and adrenal medulla using stem cell models in the laboratory. Cells capable of forming these two organs are used as examples to investigate the development of nephroblastoma and neuroblastoma. Although these organs are located close together in the embryo, they arise from different cell layers. “It is important to compare two regions with different developmental origins,” says Halbritter. Only by doing so can researchers determine what distinguishes the cells at relevant developmental stages and why cells with the same genetic mutation mature into a healthy organ in one case and promote tumor formation in the other organ.

Collaboration with International Stem Cell Experts

In this project, Halbritter collaborates with internationally renowned developmental biologists Anestis Tsakiridis (University of Sheffield, UK) and Minoru Takasato (RIKEN, Japan). Close collaboration is also planned with Sabine Taschner-Mandl, an expert in solid tumors in children with a focus on neuroblastoma and Principal Investigator at St. Anna Children’s Cancer Research Institute.

The four-year study builds upon previous research of Halbritter’s group, and a workshop on stem cells and neuroblastoma was conducted in December 2023 as part of the preparation. “Therapy development for children with cancer has been very successful. However, many treatments are rather non-specific and come with side effects,” explains Halbritter. Therefore, understanding the origin and development of a tumor is crucial for specific treatment and minimizing side effects.