Complex in vitro 3D models of digestive system tumors to advance precision medicine and drug testing: Progress, challenges, and trends

Pharmacol Ther. 2022 Nov:239:108276. doi: 10.1016/j.pharmthera.2022.108276. Epub 2022 Aug 31.

Abstract

Digestive system cancers account for nearly half of all cancers around the world and have a high mortality rate. Cell culture and animal models represent cornerstones of digestive cancer research. However, their ability to enable cancer precision medicine is limited. Cell culture models cannot retain the genetic and phenotypic heterogeneity of tumors and lack tumor microenvironment (TME). Patient-derived xenograft mouse models are not suitable for immune-oncology research. While humanized mouse models are time- and cost-consuming. Suitable preclinical models, which can facilitate the understanding of mechanisms of tumor progression and develop new therapeutic strategies, are in high demand. This review article summarizes the recent progress on the establishment of TME by using tumor organoid models and microfluidic systems. The main challenges regarding the translation of organoid models from bench to bedside are discussed. The integration of organoids and a microfluidic platform is the emerging trend in drug screening and precision medicine. A future prospective on this field is also provided.

Keywords: Digestive system cancer; In vitro 3D models; Organoids; Tumor microenvironment; cancer-on-a-chip.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Digestive System Neoplasms* / pathology
  • Gastrointestinal Neoplasms* / pathology
  • Humans
  • Mice
  • Organoids / pathology
  • Precision Medicine
  • Tumor Microenvironment