Tumor Organoids: The Era of Personalized Medicine

Biochemistry (Mosc). 2024 Jan;89(Suppl 1):S127-S147. doi: 10.1134/S0006297924140086.

Abstract

The strategies of future medicine are aimed to modernize and integrate quality approaches including early molecular-genetic profiling, identification of new therapeutic targets and adapting design for clinical trials, personalized drug screening (PDS) to help predict and individualize patient treatment regimens. In the past decade, organoid models have emerged as an innovative in vitro platform with the potential to realize the concept of patient-centered medicine. Organoids are spatially restricted three-dimensional clusters of cells ex vivo that self-organize into complex functional structures through genetically programmed determination, which is crucial for reconstructing the architecture of the primary tissue and organs. Currently, there are several strategies to create three-dimensional (3D) tumor systems using (i) surgically resected patient tissue (PDTOs, patient-derived tumor organoids) or (ii) single tumor cells circulating in the patient's blood. Successful application of 3D tumor models obtained by co-culturing autologous tumor organoids (PDTOs) and peripheral blood lymphocytes have been demonstrated in a number of studies. Such models simulate a 3D tumor architecture in vivo and contain all cell types characteristic of this tissue, including immune system cells and stem cells. Components of the tumor microenvironment, such as fibroblasts and immune system cells, affect tumor growth and its drug resistance. In this review, we analyzed the evolution of tumor models from two-dimensional (2D) cell cultures and laboratory animals to 3D tissue-specific tumor organoids, their significance in identifying mechanisms of antitumor response and drug resistance, and use of these models in drug screening and development of precision methods in cancer treatment.

Keywords: 3D tumor organoids; chemotherapy; immune checkpoints; immunotherapy; induced pluripotent stem cells (iPSCs); patient-derived tumor organoids (PDTOs); personalized therapy; precision medicine; programmed cell death; targeted therapy.

Publication types

  • Review

MeSH terms

  • Animals
  • Drug Evaluation, Preclinical
  • Humans
  • Neoplasms* / drug therapy
  • Neoplasms* / metabolism
  • Organoids
  • Precision Medicine*
  • Tumor Microenvironment