Abstract 1628: Application of conditionally reprogrammed cell in cancer model establishment and new target identification

Abstract

Abstract Tumor cell immortalization through conditional reprogramming, particularly from limited biopsy specimen, is an invaluable tool to generate propagating tumor cells for cell-based drug sensitivity assay and bio-banking in vitro. We have successfully reprogrammed primary tumor cells from a number of tumor types, including lung carcinoma, breast cancer and glioma .etc. The conditionally reprogrammed cells exhibited typical colonized growth, which is well maintained upon cryopreservation. In some cases, the cells can be passaged for multiple times and likely become stable cell lines. We attempt to extend conditional reprogrammed tumor cells to reconstitute and grow PDX models in vivo and find the tumor formation rate is much higher than the primary tissue’s. This attempt provides a new process for establishing PDX models from variant types of cancer, especially the cancer types with low success rate in PDX establishment. We also establish PDX-derived cell lines by conditional reprogramming, which could be used in in vitro drug efficacy study and anti-cancer drug target identification. Functional library screening, such as genome-wide CRISPR/Cas9 library or specific pro-siRNA library screening, could discover new targets directly by evaluating the effect of the knockout/knockdown of specific genes. We have established several cell lines from drug resistant PDX, including Osimertinib and other targeted drugs resistant models, and found potential targets by pro-siRNA library screening. These potential targets could be validated on the matching cell line and PDX and the matching in vitro and in vivo tools will also enhance the further research of new targeted small molecules or antibodies. Citation Format: Yuan Long, Le Li, Shizhu Zhao, Song Xi, Danyi Wen. Application of conditionally reprogrammed cell in cancer model establishment and new target identification [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1628.