New study adds important insights into complex childhood cancer
Researchers in the group of Associate Professor Ninib Baryawno, Department of Women's and Children's Health, KI, have made significant strides in the fight against pediatric cancer by studying tumors of the nervous system, particularly neuroblastoma. The study is published in Cancer Research, the journal of the American Association for Cancer.
Neuroblastoma, a heterogeneous and complex pediatric cancer, lies at the core of the research group’s efforts. Its wide variation in chemosensitivity and resistance presents a major challenge to developing effective treatments.
Exploring the complexity of pediatric cancer
By combining basic and translational research, the Baryawno Lab utilizes advanced technologies such as single-cell analysis and functional preclinical testing to explore the role of the tumor microenvironment in cancer progression, metastasis, and therapy resistance.
"One of the biggest barriers in creating new cancer therapies is the development of preclinical models that accurately reflect human disease," says the first author Bethel Embaie, PhD student at the Department of Women's and Children's Health, KI, explains.
To address this, the group has studied genetically engineered models that spontaneously develop neuroblastoma while maintaining an intact immune system. Using single-cell RNA sequencing, they have analyzed tumor tissues at an unprecedented resolution, mapping the diverse cellular and molecular components of the tumor and its microenvironment.
These insights have enabled the creation of ex vivo tumoroid models that faithfully replicate the complexity of patient tumors.
The next steps in the fight against cancer
The future of this research is promising. The next steps include utilizing the tumoroid culture systems for high-throughput drug screening and CRISPR-based functional genomics studies. The group also aims to expand the platform to model metastatic disease in neuroblastoma and create patient-derived xenograft (PDX) organoids.
"These advancements will not only accelerate the discovery of effective cancer therapies but also bring us closer to personalized treatment strategies for pediatric tumors," says Bethel Embaie.
Publication
“Comparative Single-Cell Transcriptomics of Human Neuroblastoma and Preclinical Models Reveals Conservation of an Adrenergic Cell State”, Bethel Tesfai Embaie, Hirak Sarkar, Adele Mirna. Alchahin, Jörg Otte, Thale Kristin Olsen, Conny Tümmler, Polina Kameneva, Artem V. Artemov, Natalia Akkuratova, Igor Adameyko, Jan-Bernd Stukenborg, Malin Wickström, Per Kogner, John Inge Johnsen, Shenling Mei, Peter V. Kharchenko, Ninib Baryawno. Cancer Research, online January 14, 2025. Doi: 10.1158/0008-5472.CAN-24-1507.