Tech Session III: Nanomedicine and Nanoscale Delivery (Nano)
MUC4-Targeted Nanoparticles Deliver MRTX1133 and MDP5 to Overcome Pancreatic Cancer Chemoresistance
Wednesday, July 16, 2025
11:27 AM – 11:38 AM EDT
Introduction: Pancreatic ductal adenocarcinoma (PDAC) has an 11% 5-year survival rate, with >90% harboring KRAS mutations, primarily G12D (40%). MRTX1133, a selective KRAS G12D inhibitor, shows efficacy in PDAC models. However, resistance mechanisms, such as EGFR/HER2 upregulation and PI3K pathway activation, limit its effectiveness. Co-targeting KRAS and PI3Kα may overcome resistance in KRAS G12D-driven PDAC. Our in-house synthesized MDP5, a novel BRD4 and PI3K dual inhibitor, overcomes MRTX1133-induced chemoresistance, enhancing anti-tumor activity both in vitro and in vivo.
Learning Objectives:
At the completion of this activity, participants will know
Combining MRTX1133 and MDP5 targets KRAS G12D, BRD4, and PI3K, overcoming PDAC resistance.
MRTX1133 and MDP5 synergistically reduce KRAS-associated gene expression and tumor volume in models.
