HDAC5 Deficiency Induces Intrinsic Resistance to KRASG12D Inhibition by Disrupting c-Myc Acetylation-Ubiquitination Homeostasis [RNA-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: RNA-seq analysis was performed on tumors from KPC WT and Hdac5 KO mice, as well as on PANC-1 cells transfected with shNC or shHDAC5, to investigate transcriptomic changes following HDAC5 knockdown.