Targeting class I HDACs suppresses oncogenic vulnerabilities and potentiates KRAS/MAPK pathway inhibitors in KRAS-mutant cancers - PubMed
5 days ago
- #HDAC inhibitors
- #epigenetic therapy
- #KRAS-mutant cancers
- Class I HDAC inhibitors (HDACi) show efficacy in KRAS-mutant cancers, overcoming resistance to KRAS inhibitors.
- The novel inhibitor IHCH9033 induces p53 and c-Myc acetylation, leading to oxidative stress, DNA damage, and apoptosis.
- IHCH9033 suppresses the YAP-c-Myc axis and synergizes with KRAS/MAPK inhibitors to enhance tumor suppression.
- The combination therapy targets both epigenetic and oncogenic pathways, showing promise in resistant models.
- IHCH9033 demonstrates brain bioavailability and reduces metastasis in NSCLC and PDAC models.