Combination of PARP and KRASG12D inhibitors enhances therapeutic efficacy by exploiting vulnerabilities in PDAC - PubMed
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- Combination of PARP and KRASG12D inhibitors enhances therapeutic efficacy in PDAC.
- KRASG12D blockade suppresses HR repair by downregulating BRCA1, RAD51, and RPA32, leading to HR deficiency.
- Combined MRTX1133 (KRASG12D inhibitor) and olaparib (PARP inhibitor) treatment shows synergistic cytotoxicity in vitro and durable tumor regression in vivo.
- The combination therapy remodels the tumor immune microenvironment, enhancing CD8+ T-cell infiltration.
- Co-targeting KRASG12D and PARP exploits induced DNA-repair vulnerability for synthetic lethality in KRASG12D-driven PDAC.