Abstract 5205: B6- KrasLSL-G12C mouse model for assessing the occurrence and development of lung and pancreatic cancer tumors

Abstract In May 2021, the FDA approved sotorasib (Lumakras™) as the first treatment for adult patients with non-small cell lung cancer (NSCLC) harboring the KRASG12C genetic mutation. To study the relationship between the mutational activation of KRAS and tumorigenesis, and promote the development o...

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Published inCancer research (Chicago, Ill.) Vol. 83; no. 7_Supplement; p. 5205
Main Authors Yang, Xiaoliu, Jiang, Yunlong, Wu, Xue, Zhang, Mingkun, Zhao, Jing, Chen, Santi Suryani, Li, Zhiying, Trujillo, Erica, Moore, Mark Wade, Gao, Xiang, Ju, Cunxiang
Format Journal Article
LanguageEnglish
Published 04.04.2023
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Summary:Abstract In May 2021, the FDA approved sotorasib (Lumakras™) as the first treatment for adult patients with non-small cell lung cancer (NSCLC) harboring the KRASG12C genetic mutation. To study the relationship between the mutational activation of KRAS and tumorigenesis, and promote the development of KRAS-G12C inhibitors, we established the B6-Loxp-Stop-Loxp Kras G12C (B6-KrasLSL-G12C) strain. Upon induction of Cre recombinase, floxed Stop sequences will be deleted in the mouse genome, and the oncogenic KRAS-G12C protein will be expressed at endogenous levels allowing for control of the timing and location of tumor initiation. The C57BL/6-KrasLSL-G12C mice were crossed with the Lyz2-cre mice to develop a spontaneous lung cancer model. KRAS G12C mutant could be detected in type II alveolar epithelial cells (ATII). Furthermore, these mice develop lung cancer at 8-10 weeks of age. In addition, when B6-KrasLSL-G12C mice were crossed with the B6-P53LSL-R172H and Ptf1/p48-Cre mice, the offspring developed pancreatic cancer after 10-12 weeks of tamoxifen treatment. In conclusion, B6-KrasLSL-G12C mice can be used to study the occurrence and development of pancreatic and lung cancer, as well as the potential applications of cancer therapies. Citation Format: Xiaoliu Yang, Yunlong Jiang, Xue Wu, Mingkun Zhang, Jing Zhao, Santi Suryani Chen, Zhiying Li, Erica Trujillo, Mark Wade Moore, Xiang Gao, Cunxiang Ju. B6-KrasLSL-G12C mouse model for assessing the occurrence and development of lung and pancreatic cancer tumors. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5205.
ISSN:1538-7445
1538-7445
DOI:10.1158/1538-7445.AM2023-5205