Quantitative MRI Measurements Record Pancreatic Cancer and Stroma Reactions to New KRAS Inhibitor

Abstract

Motivation: KRAS mutations occur in 90% of pancreatic ductal adenocarcinoma(PDA) with G12Dmutation being the most common.Recent KRAS(G12D) inhibitors have unraveled an exciting therapeutic opportunity for this deadly cancer,as they are being tested in clinical trials. Goal(s): However, the prior use of KRAS(G12C)inhibitors in lung cancer treatment showed mere 50% patient response,despite the accurate genetic mutation,calling for biomarkers which can assess the drug-target engagement early on and predict treatment outcome. Approach: To test the utility of translational MRI markers in a clinically relevant PDA model for early responses to KRAS(G12D) inhibitor,MRTX1133. Results: ADC,Ktrans and MTR captured MRTX1133 induced early cancer cell death and stroma change. Impact: Our study in genetically engineered mouse model of pancreatic cancer supports that clinical translatable MRI metrics (ADC, Ktrans and MTR) are promising for capturing early pharmacodynamic responses to KRAS inhibitor MRTX1133.