Mutations in the ATRX gene, which occur in many gliomas, alter DNA structure and chromatin interactions. This activates cancer-promoting signaling pathways that drive tumor growth. This is shown by a study from the MD Anderson Cancer Center.
Researchers led by Jason Huse and Kunal Rai found that the loss of ATRX not only causes random damage but specifically reprograms gene regulation. The HOXA, WNT5A, and SLITRK6 signaling pathways are particularly affected. These promote cancer cell migration and tumor growth.
In preclinical models, the growth of ATRX-mutated gliomas could be significantly slowed by blocking the HOXA signaling pathway with the peptide HXR9. The animals lived longer. Inhibition of WNT5A and SLITRK6 also reduced tumor cell motility.
"ATRX mutations are a defining feature of many gliomas. Our results show that the loss of ATRX not only causes random damage but specifically reprograms the architecture of gene regulation," explained Jason Huse.
The study was published in the journal Nucleic Acids Research. The findings open up new therapeutic approaches for patients with ATRX-mutated gliomas by focusing on the functional consequences of the mutation.
