Abstract
Abstract Defining the effect of specific oncogenic mutations on tumor behavior and therapy response is essential for developing effective treatment strategies and realizing the promise of precision medicine. KRAS is the most frequently mutated oncogene in human cancers, and specific cancer types show a clear bias in the types and frequency of Kras alterations. The generation of conditional animal models, such as Lox-Stop-Lox (LSL) KrasG12D (KC model) and LSL-KrasG12Vgeo mice, has provided important tools to dissect the impact of Kras mutation in tumor development, but these models alone do not recapitulate the spectrum of Kras alterations in human cancer. To better reflect this Kras mutational landscape, we have developed a series of critical LSL-Kras mouse models that recapitulate common Kras alterations observed in colorectal (G13D), pancreatic (G12R), and lung cancer (G12C). Mice carrying each LSL-Kras variant, a pancreas-specific Cre (p48-Cre) and a far-red fluorescent Cre-reporter (mKate2), displayed drastically different morphologic features in early stages of pancreatic cell transformation, associated with dramatic changes in the degree of stromal expansion within the pancreas. Now, we are focused in exploring how such changes following Kras alterations influence progression to carcinoma and response to targeted therapies. Citation Format: Maria Paz Zafra Martin, Direna Alonso-Curbelo, J. Erby Wilkinson, Emma Schatoff, Lukas E. Dow. Specific Kras codon 12 and 13 mutations display different tumor initiation in pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference on Targeting RAS-Driven Cancers; 2018 Dec 9-12; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(5_Suppl):Abstract nr A49.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call