Advancing cancer research through organoid technology

Abstract

The complexity of tumors and the challenges associated with treatment often stem from the limitations of existing models in accurately replicating authentic tumors. Recently, organoid technology has emerged as an innovative platform for tumor research. This bioengineering approach enables researchers to simulate, in vitro, the interactions between tumors and their microenvironment, thereby enhancing the intricate interplay between tumor cells and their surroundings. Organoids also integrate multidimensional data, providing a novel paradigm for understanding tumor development and progression while facilitating precision therapy. Furthermore, advancements in imaging and genetic editing techniques have significantly augmented the potential of organoids in tumor research. This review explores the application of organoid technology for more precise tumor simulations and its specific contributions to cancer research advancements. Additionally, we discuss the challenges and evolving trends in developing comprehensive tumor models utilizing organoid technology.

Keywords: Gene editing; In vitro modeling; Multi-omics analysis; Precision medicine; Tumor microenvironment; Tumor organoids.

Fig. 1

Potential applications of tumor organoids in cancer research: (A) To simulate the tumor microenvironment in vitro, the microenvironment conditions are replicated, and the interaction between tumor cells and various cell types in the surrounding microenvironment is investigated. (B) Relevant data from multidimensional sources, including the analysis and extraction of information from multi-omics data such as genomics, transcriptomics, proteomics, and monocytosis is integrated into organoids. (C) Tumor organoids can be utilized for tumor modeling, enabling prospective drug sensitivity testing and prediction of drug response to achieve precision treatment through the establishment of a biobank. (D) Tumor organoids, when combined with advanced imaging, enhance the precision and efficiency of cancer research. (E) The application of gene editing tools involves targeted modification of genes in organoids and the introduction of specific gene or pathway changes to study the occurrence and development of tumors and tumor modeling

Fig. 2

Cell sources of tumor organoids include surgical samples, needle biopsy tissues, and malignant ascites. The constructed tumor organoids can be introduced into different platforms to mimic TME: (A) Co-culture model: exogenous stromal cells from the tumor micro-environment; (B) The air-liquid interface: when cultured in the Transwell chamber, an air-liquid interface can be formed, which can reproduce the tumor immune microenvironment. (C) Microfluidicchip: controls the changes of environmental conditions and nutrient delivery in the TME, and reconstructs the fluid characteristics, mechanical tensile force, immune infiltration, and other complex elements in the TME; (D) Bioprinting: involves the use of bioactive materials to form bionic and composite TME in vitro

Fig. 3

A data model of tumor organoids is constructed to comprehensively characterize the relationship between tumor and model, disease biomarkers and potential therapeutic targets are identified, and cell behavior and drug response are predicted

Fig. 4

Gene Editing of Organoids Using Genome Editing Methods involves Crispr/cas9 editing technology and base editing technology for studying the occurrence of tumors and the development of tumor models