Recent research has uncovered significant genetic links between neural tube defects (NTDs) and glioblastoma (GBM), highlighting the roles of two specific genes, Poli and Fgf1, as potentially pivotal players in both developmental abnormalities and cancer. These findings stem from the work of scientists at Shanxi Medical University and Shanxi Cancer Hospital, who employed advanced bioinformatics and molecular techniques to investigate how these genes may contribute to both NTDs and GBM.
The study, published on January 31, 2025, seeks to bridge the gap between embryonic development and cancer tumorigenesis by identifying common genetic markers. NTDs, which include severe malformations such as spina bifida, occur when the neural tube fails to close properly during embryonic development. Similarly, glioblastoma is one of the most aggressive forms of brain cancer and is believed to originate from neuroectodermal cells.
The researchers utilized transcriptome sequencing data from RA-induced NTD mouse models, human NTD samples, and GBM tumors. Through this analysis, they identified 162 genes associated with NTDs and GBM. Among them, Poli and Fgf1 emerged as key targets, verified at both the mRNA and protein levels.
Poli is involved in DNA repair processes, which are critically important during embryonic growth. Fgf1 plays a role in cell proliferation and differentiation, particularly within the neural tube. The expression of both genes was found to be aberrant across developmental stages and in tumor samples, indicating their potential utility as biomarkers for diagnosing and treating these conditions.
One of the most exciting aspects of the research is the identification of pazopanib, a small molecule drug known for its anti-tumor properties. The research team discovered through molecular docking studies and cytological experiments, pazopanib can effectively target Fgf1, inhibiting the proliferation of GBM tumor cells and promoting apoptotic mechanisms. It appears to have no significant effect on the migratory capabilities of cells, which could position it as a therapeutic option for GBM without exacerbation of metastasis.
These findings underline the complex relationships between early development and cancer, presenting the possibility of new treatment strategies for both conditions. Further research on the interaction networks involving these genes may shed light on novel therapeutic avenues. Given the high mortality associated with both NTDs and glioblastoma, advancing our comprehension of their shared genetic underpinnings holds great promise for improving clinical outcomes.
This discovery could lead to innovative approaches not only to detect and diagnose neural tube defects before birth but also to develop targeted therapies for glioblastoma, potentially changing the prognosis for patients affected by these serious health challenges.