Abstract 5032: Tumor in a Dish (TiD): Novel approach for precision therapy using patient-derived cells

Abstract

Metastatic colorectal cancer is a major cause of cancer-related deaths. Most patients with metastatic disease fail to respond to current chemotherapeutic agents. Current, traditional culture model is not appropriate to study the metastatic disease in in vitro condition. Hence, there is an ominous need for developing new therapeutic and preventive agents that can target metastatic cancer. Unfortunately, there are no good in vitro as well as in vivo models available for studying metastatic disease. Hence, in this abstract, we demonstrate the development of a new lung model system, called Primitive Lung in a Dish or PLiD with cancer cells called “Tumor in a Dish” or TiD. The PLiD system shows expression of specific cell type marker like E-cadherin (epithelial cell) vimentin (fibroblast), CD31 (heme-endothelial cells) and LYVE1 (lymph-endothelial cells). Interestingly, we showed expression of lung functional protein like surfactant protein B and D. In the multicell type TiD system, cancer cells were grown in a 3-dimensional (3D) PLiD system containing normal epithelial cells, fibroblasts and endothelial cells. The model resembles in vivo tumor microenvironments, including cell-cell contact, tumor architecture, and the influence of different cell types. We next determined the efficacy of standard colon cancer chemotherapeutic agents. We observed differential activity of 5FU in TiD system when compared to standard 2D and single-cell type 3D cultures. Another surprising result we found was with freshly isolated colon cancer cells from patient samples. Without knowing the genetic characteristics of the cancer tissue, the TiD system was able to identify cells that were resistant to oxaliplatin. Moreover, using this method, we have developed novel drugs that target cancer cells while not affecting the normal tissue. More importantly, the technique has significant utility in precision/personalized medicine, wherein this phenotypic screen can be coupled with current DNA pharmacogenetics to identify the ideal therapeutic agent, thereby increasing the probability of response to treatment while reducing unnecessary side effects. Citation Format: Prabhu Ramamoorthy, Sufi Thomas, Sathish Ramalingam, Gaurav Fnu, Sita G. Sittampalam, Roy A. Jensen, Shrikant Anant. Tumor in a Dish (TiD): Novel approach for precision therapy using patient-derived cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5032.