Exploiting rDNA loci vulnerabilities to treat incurable cancers driven by chromatin mutations

Cancers driven by mutations in chromatin modifiers, including brain and bone cancers, and leukemias, are linked to poor prognoses and remain largely untreatable with existing therapies. Our preliminary data, focused on ATRX/H3.3 mutant cancers, show that dysregulation of ribosomal DNA (rDNA) genes creates a vulnerability in these cancers, making them more sensitive to RNA Polymerase I inhibitors,supporting a therapeutic rationale and insights into cancer development