Advancing cancer research through organoid technology

Zeng et al. Journal of Translational Medicine https://doi.org/10.1186/s12967-024-05824-1 (2024) 22:1007 Journal of Translational Medicine Open Access REVIEW Advancing cancer research through organoid technology Guolong Zeng1†, Yifan Yu1†, Meiting Wang1†, Jiaxing Liu1, Guangpeng He1, Sixuan Yu1, Huining Yan1, Liang Yang1,2*, Hangyu Li1,2* and Xueqiang Peng1,2* 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 Tumor organoids, In vitro modeling, Tumor microenvironment, Multi-omics analysis, Gene editing, Precision medicine Introduction As one of the major health threats, cancer continue to have high morbidity and mortality rates. Despite significant advances in the understanding of tumor mechanisms, standard cancer treatments have made only limited progress [1]. In this context, in vitro and in vivo † Guolong Zeng, Yifan Yu and Meiting Wang contributed equally to this work. *Correspondence: Liang Yang Hangyu Li Xueqiang Peng 1 Department of General Surgery, The Fourth Affiliated Hospital, China Medical University, Shenyang 110032, China 2 Shenyang Clinical Medical Research Center for Diagnosis, Treatment and Health Management of Early Digestive Cancer, Shenyang, China experimental models, such as cancer cell lines, animal models, and patient-derived tumor xenografts (PDTX), have significantly advanced tumor research [2, 3]. However, there are many limitations in these models. Traditional cancer cell lines are cultured in a two-dimensional environment, which limits their ability to mimic the natural growth pattern and behavior of tumor cells in 3D space [4]. Similarly, long-term culture can lead to genetic drift, resulting in a loss of heterogeneity and failing to fully represent the complex biology of human tumors [5]. Animal models and PDTX models are significantly different from humans in genetic, physiological, and metabolic aspects, which are easily restricted by species differences and ethical issues [6, 7]. Moreover, cancer cell lines have several disadvantages, such as the absence of the tumor’s complex surrounding environment, challenges in establishing repositories, and the significant economic and time costs associated with experimental animal studies © The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Zeng et al. Journal of Translational Medicine (2024) 22:1007 [8, 9]. Given these challenges, developing in vitro models that can more accurately simulate the characteristics of human tumors in vivo has become a crucial need in cancer research [10]. In this context, the development of in vitro models that can more precisely replicate the characteristics of human tumors in vivo has become a crucial focus in cancer research. Tumor organoids, emerging as a pivotal research area, are gaining widespread attention Page 2 of 17 and are being increasingly utilized in various aspects of tumor research (Fig. 1). Organoids, cultured in vitro, are 3D microstructures capable of self-organization and renewal, enabling them to replicate the essential functions, structure, and biological intricacies of organs. Derived primarily from induced pluripotent stem cells (iPSCs) or tissue-derived cells (TDCs), these organoids encompass various cell types, such as normal stem/progenitor cells, differentiated cells, 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 Zeng et al. Journal of Translational Medicine (2024) 22:1007 and cancer cells [11, 12]. By utilizing patient-derived primary human cancer tissue to develop patient-derived tumor organoid (PDTO) models in vitro under 3D cultivation conditions, these organoids effectively simulate the growth of the primary tumor microenvironment in patients. This model can simulate tumor samples with precise spatial structure and histomorphology, while also preserving the heterogeneity of the primary tumor to some degree [13]. These “microtumors” offer several advantages in tumor research: [1] They replicate the development and progression of cancer in vitro; [2] They retain the phenotypic traits of the original tumor; [3] They offer matched normal tissue controls for comparison; [4] They can reconstruct the tumor microenviron (...truncated)