HDAC5 Deficiency Induces Intrinsic Resistance to KRASG12D Inhibition by Disrupting c-Myc Acetylation-Ubiquitination Homeostasis [ChIP-Seq]

We found that HDAC5 deletion significantly enhances intrinsic resistance to MRTX1133 in KRASG12D mutant pancreatic cancer. Mechanistic studies show that HDAC5 deletion promotes resistance to KRASG12D inhibitors by sustaining the activation of the MAPK signaling pathway. Overall design: ChIP-seq was performed on PANC-1 cells transfected with shControl-1,shControl-2,shHDAC5-1, or shHDAC5-2 to investigate the impact of HDAC5 knockdown on MYC chromatin binding.