ENA 2024 Poster PB262

Development of Patient-Derived Colorectal Cancer Xenograft and Organoid Models with Acquired Resistance to KRAS^G12C Inhibitors

Aaron L. Hua, Jitai Zheng, Limei Shang, Jinxi Wang, Wubin Qian, Yi Sun, Ludovic Bourre, Jessie J.J. Wang

The KRAS^G12C mutation is found in 14% of non-small cell lung cancer (NSCLC) and 3% of colorectal cancer (CRC). Adagrasib (MRTX849) and sotorasib (AMG510), FDA approved KRAS^G12C inhibitors, have shown promising results in NSCLC and modest efficacy in CRC. Despite the encouraging efficacy, acquired resistance, such as secondary KRAS mutations including G12D, Y96D, Q61H, has limited their clinical benefits.

In this study we introduced CRC PDX and PDXO models, that have been successfully developed from longitudinal tumor tissues from a single patient including acquired resistance to MRTX849 treatment, showcasing their potential to serve as valuable preclinical translational models to evaluate the next-generation KRAS^G12C  inhibitors and innovative combination strategies.

Download this Poster to Discover:

• A set of longitudinal pretreated PDX models with acquired resistance to KRAS^G12C  inhibitors.
• How matched organoids can be generated from PDX models and show similar response to PDX data, making them a valuable tool for in vitro studies.

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