Domestic researchers revealed a new mechanism that simultaneously induces differentiation and apoptosis of cancer stem cells in glioblastoma, a representative form of intractable brain tumors.
The National Research Foundation of Korea (NRF) announced on the 20th that a research team led by Professor Kim Hyung-gi from Korea University and Professor Park Jong-hwi from Gachon University has identified that the DHRS13 protein, which mainly exists in mitochondria, allows brain tumor stem cells to maintain an undifferentiated state. The results of this research were published online on July 30 in the international scientific journal 'Nature Communications.'
Glioblastoma is a type of brain tumor with very poor prognosis due to intratumoral heterogeneity and strong treatment resistance. In particular, undifferentiated brain tumor stem cells play a crucial role in tumor dissemination and recurrence. Existing treatments have involved administering differentiation-inducing substances from outside, but they have significant side effects affecting normal cells and limited effectiveness in solid tumors.
The research team identified DHRS13, one of the metabolic genes commonly highly expressed in an undifferentiated state, through transcriptome analysis of brain tumor stem cells. DHRS13 converts a substance called retinal into retinol, inhibiting the production of retinoic acid. As a result, it obstructs retinoic acid receptor signaling, interfering with the differentiation of brain tumor stem cells.
In fact, inhibiting DHRS13 led to the accumulation of retinoic acid within cells, prompting differentiation within three days. Subsequently, mitochondrial reactive oxygen species surged, resulting in structural damage and large-scale autophagy, which induced cell death. In animal experiments, tumor growth inhibition and extended survival were observed in mice implanted with DHRS13-inhibited cancer stem cells.
However, this study has only demonstrated that inhibiting DHRS13 can selectively eliminate cancer stem cells at the cellular and animal levels. Future research is needed to determine whether the same mechanism operates across various cancer types and to verify safety and efficacy for clinical application. Additionally, developing drugs that can directly inhibit DHRS13 and conducting pharmacokinetic and toxicity assessments remain as future tasks.
Professor Kim Hyung-gi noted, "This research presented a new therapeutic target that can induce differentiation and apoptosis simultaneously by regulating the metabolic pathways within brain tumor stem cells without external drug administration," and added, "This could minimize side effects on normal cells while selectively eliminating only cancer cells, serving as a foundation for developing next-generation targeted therapies that suppress recurrence and metastasis in glioblastoma as well as various solid tumors."
References
Nature Communications (2025), DOI: https://doi.org/10.1038/s41467-025-62148-4