Abstract 26: BaF3 RAS cell panel, a powerful cell model for Ras inhibitor discovery and development

Abstract

Abstract RAS, abbreviated from Rat sarcoma virus, is composed of three small GTPase proteins, HRAS, KRAR and NRAS. Over-activation of these genes due to different mutation were found in up to 20% of all human cancers and about 90% in pancreatic cancer. The identification of RAS mutation, especially KRAS-G12S or G12D mutation, as cancer diver genes has recently led to rapid development of anti-tumor therapeutics agents such as sotorasib (AMG 510), adagrasib (MRTX-849) and MRTX1133, but there are still no good drugs for the cancer patients with other RAS mutations. Ba/F3 line is a popular cell model for studying both kinases and their inhibitors, because some kinases can render the growth of Ba/F3 cells to be depended on the over-activation of the kinases instead of exogenous IL-3 supplement, while their inhibitors can antagonize these effects. Our group has generated a Ba/F3 RAS cell panel with 29 KRAS, 11 HRAS and 20 NRAS different single or double mutants for RAS inhibitor screening and development, all of these lines were well validated with PCR sequencing, Western Blot and KRAS G12C and G12D inhibitors. In addition to use the cell lines for in vitro assays, the transformed Ba/F3 lines can grow well in immune-deficient mice as in vivo models. Our data indicate that the cell line panel of Ba/F3 is a powerful system for new RAS inhibitor discovery and development. Citation Format: PENG YAO, Yu Wang, Chang Liu, Na Wang, Wei Meng, Jinying Ning, Feng Hao. BaF3 RAS cell panel, a powerful cell model for Ras inhibitor discovery and development [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 26.