GRANTS. Researcher Helena Carén studies cancer stem cells to understand why malignant gliomas are so difficult to treat. The goal is to develop a better treatment with fewer side effects. She is among the researchers in Gothenburg sharing SEK 15 million in research funding from the Swedish Childhood Cancer Fund.
A major problem with brain tumors is the risk of relapse, which is often difficult to remedy. Researchers believe the tumor relapses can be traced to cancer stem cells, which appear to withstand treatment.
To find a more effective treatment, Helena Carén at the Sahlgrenska Cancer Center in Gothenburg seeks to understand the behavior of cancer stem cells in malignant gliomas, central nervous system tumors that afflict a few children every year.
She suspects that errors in what is known as epigenetic regulation drive the development of brain tumors. The epigenetic processes instruct the cells which genes in our DNA are to be expressed in the various organs of the body. This regulation plays an important role in determining which proteins the cells form.
“Errors in these mechanisms occur in essentially all types of tumors,” says Carén.
Her research team is working on a model in which stem cells have been isolated from tissue in patients who have undergone surgery for a brain tumor. The stem cells can then be studied to find out what went wrong and how the epigenetic regulation can be influenced.
This work uses the new Crispr-Cas9 technology. It acts as “gene scissors” that can cut and edit the DNA sequences. Using this technique, researchers can systematically deactivate various genes to identify which protein expressions the tumor’s stem cells depend on.
“We want to disable genes and see when the cells no longer grow. This indicates that we have knocked out an important gene that the tumor needs.”
Helena Carén also investigates how normal neural stem cells are affected by different gene expressions. “The goal is to find something specific for the tumor cells that can be attacked with treatment but that does not strike all cells and cause side effects as a result.”
The Swedish Childhood Cancer Fund is funding the research, which requires expensive whole-genome sequencing, for the next three years.
“The Childhood Cancer Fund’s support means that we can carry out the study. We cannot cure these children today, so new treatment is urgently needed.”
She will receive SEK 1.5 million for her project over three years and also SEK 1 million for a clinical project grant to improve diagnostics of brain tumors in children using DNA methylation-based classification.
Full list of recipients from Gothenburg who have received funding from the Swedish Childhood Cancer Fund:
- Helena Carén: Improved diagnosis of brain tumors in children using DNA methylation-based classification and focusing on cancer stem cells to understand high-grade glioma in children
- Linda Fogelstrand: High-sensitivity analysis of leukemia cells in acute myeloid leukemia – a tool for treatment management
- Magnus Dahlander (development): Nationally coordinated patient information on cytostatics for children with cancer and their parents
- Lars Palmqvist: Determine the incidence, prognosis and mechanisms of acute myeloid leukemia with the translocation t(7;12)(q36;p13)
- Tanmy Mondal: Human trunk neural cells: A model system for understanding neuroblastoma development
- Ruth Palmer: Functional relevance of anaplastic lymphoma kinase (ALK) and its ALKAL1/2 ligands in neuroblastoma
- Frida Abel: Genetic markers in nerve cell tumors – relevance for clinical diagnostics and treatment
- Magnus Sabel: International treatment protocols for medulloblastoma (Sheltered Instruction Observation Protocol [SIOP] high-risk medulloblastoma and SIOP PNET 5 medulloblastoma)
- Jikui Guan: RAS-MAPK signaling in neuroblastoma
- Tommy Martinsson: The neuroblastoma genome: Stratification, biomarker identification and new therapy goals
- Karin Mellgren: Circulating tumor DNA as biomarker in childhood cancer
TEXT: CHARLOTTE DELARYD / SWEDISH CHILDHOOD CANCER FUND
PHOTO: MALIN ARNESSON