Although significant advances have been made in some types of childhood cancer, high-grade gliomas still lack effective treatment.
30-60% of these Pediatric brain tumor There is a mutation in the gene H3F3A. This gene contains a encoded blueprint for histone H3.3, which plays an important role in the structure of chromatin. One of these mutations is known to scientists as H3.3G34R / V. That is, the amino acid glycine, which is usually at position 34, has been replaced by arginine or valine.
Currently, an international research team led by the University of Michigan Health Rogel Cancer Center has discovered a small molecule inhibitor that can be suppressed. Tumor growth In this animal model of glioma — offers new hope for the development of treatments for pediatric patients.Their findings will be displayed in Scientific translation medicine..
“These tumors tend to develop slightly Older children It is usually between the ages of 10 and 18 rather than some of the well-known types of pediatric gliomas, “said senior research authors Sriram Venneti, MD, Ph.D., Al and Robert Glick Family Research. Professor of Pediatrics in the Department of Pathology in Michigan Medicine. “And because of the lack of effective treatments, the outlook remains pretty disastrous.”
Leading by lead author Stefan Sweha graduate student In neuroscience, the team investigated epigenetic changes in tumors, changes that are not permanent mutations in the DNA itself, but affect the way cells access and read DNA sequences. Eventually, they discovered changes due to leukemia inhibitors that led to increased secretion of a protein known as LIF. LIF then activates the STAT3 signaling pathway. It has been implicated in many other types of cancer.
A mouse model of H3.3G34R / V glioma has been shown to suppress a small molecule inhibitor of STAT3 called WP1066. tumor It grows and significantly improves the duration of survival of mice.
Drug compounds have the important property of being able to cross Blood-brain barrier, This is essential for the development of brain tumor treatments and is currently being tested in clinical trials for glioblastoma in adult patients, Venneti adds.
“Our goal is to move the compound to Clinical trial For pediatric patients, “he said.
Stefan R. Sweha et al, H3.3G34R / V Epigenetic-defined therapeutic target in high-grade glioma, Scientific translation medicine (2021). DOI: 10.1126 / scitranslmed.abf7860
University of Michigan
Quote: New clues for the treatment of pediatric brain tumors with epigenetic mutations (October 13, 2021) https: //medicalxpress.com/news/2021-10-clues-pediatric-brain-tumors-harboring.html Obtained from October 13, 2021.
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