CBIO-04DAXX INHIBITION SUPPRESSES TUMOR GROWTH IN PTEN-DEFICIENT HUMAN GLIOBLASTOMAS

Glioblastoma (GBM) is the most lethal type of brain cancer, where deletions and/or mutations in the tumor suppressor gene PTEN (phosphatase and tensin homolog) are associated to responsiveness of cancer to radiotherapy and chemotherapy. Herein, we show that a PTEN-DAXX-H3.3 chromatin complex negatively regulates proliferation and tumor growth. PTEN directly regulates oncogene expression by coordinating DAXX and histone H3.3 deposition on chromatin and in turn, DAXX protects PTEN from acetylation and ubiquitination. Furthermore, DAXX disruption in PTEN-deficient glioblastoma patient derived xenograft models suppresses tumor growth and promotes therapy sensitivity. Since PTEN loss is a common alteration in cancer, DAXX inhibition presents an approach to ablate the growth of such cancers.