Abstract 6027: Layered 3D co-cultured tumor model including vascularized stromal tissue may reflect drug sensitivities in vivo tumor

Abstract

Abstract Background: Multiple 3D culture models have been reported as a superior tumor model than 2D culture. The importance of interaction between cancer and stromal cells has been widely recognized in tumor progression and resistance to treatment. Therefore, ex vivo model recapturing the tumor microenvironment is needed to evaluate the drug efficacy under the condition imitating the patient tumor tissue. Purpose: We developed a unique 3D co-cultured tumor model with stromal tissues containing a microvascular network. Here, we investigated drug sensitivity in conventional 2D culture, our 3D co-cultured model and in vivo tumor. Methods: Drug sensitivity and gene expression on our model were evaluated using patient-derived cancer cells (PDC) established from colorectal cancer (CRC) patients in JFCR. The characteristics were compared with those of conventional 2D cultured cells or patient-derived xenograft (PDX). Results: In our 3D model, the drug sensitivities tended to be decreased in comparison with those of 2D. However, some drugs presented potent efficacy in our 3D model rather than 2D, and such drugs showed significant tumor growth suppression or tumor regression in vivo. Transcriptome profiles of our 3D model showed relatively higher similarity to those of in vivo tumors than those of 2D. Conclusion: Our study proposed the unique 3D co-cultured tumor model which may enable more accurate evaluation of drug sensitivities reflecting the in vivo circumstances. Citation Format: Yuki Takahashi, Shiro Kitano, Eiji Shinozaki, Satoshi Nagayama, Ryohei Katayama, Naoya Fujita. Layered 3D co-cultured tumor model including vascularized stromal tissue may reflect drug sensitivities in vivo tumor [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 6027.