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Targeting ACSS2 disrupts metabolic-epigenetic crosstalk to restore apoptosis and temozolomide chemosensitivity in pancreatic neuroendocrine tumors - PubMed

4 days ago
  • #ACSS2
  • #PNETs
  • #Chemoresistance
  • Targeting ACSS2 disrupts metabolic-epigenetic crosstalk to restore apoptosis and TMZ chemosensitivity in PNETs.
  • ACSS2 is upregulated in PNETs and correlates with chemoresistance by promoting histone hyperacetylation and BCL6 transcription.
  • BCL6 silences TP53, bypassing TMZ-induced G2/M arrest and suppressing apoptosis.
  • Inhibition of the ACSS2/BCL6 axis restores P53-mediated DNA damage response and TMZ sensitivity.
  • Combined ACSS2 inhibition and anti-PD1/L1 immunotherapy shows superior efficacy in PNET models.