Organoid technology and applications in cancer research

Abstract

During the past decade, the three-dimensional organoid technology has sprung up and become more and more popular among researchers. Organoids are the miniatures of in vivo tissues and organs, and faithfully recapitulate the architectures and distinctive functions of a specific organ.These amazing three-dimensional constructs represent a promising, near-physiological model for human cancers, and tremendously support diverse potential applications in cancer research. Up to now, highly efficient establishment of organoids can be achieved from both normal and malignant tissues of patients. Using this bioengineered platform, the links of infection-cancer progression and mutation-carcinogenesis are feasible to be modeled. Another potential application is that organoid technology facilitates drug testing and guides personalized therapy. Although organoids still fail to model immune system accurately, co-cultures of organoids and lymphocytes have been reported in several studies, bringing hope for further application of this technology in immunotherapy. In addition, the potential value in regeneration medicine might be another paramount branch of organoid technology, which might refine current transplantation therapy through the replacement of irreversibly progressively diseased organs with isogenic healthy organoids.In conclusion, organoids represent an excellent preclinical model for human tumors, promoting the translation from basic cancer research to clinical practice. In this review, we outline organoid technology and summarize its applications in cancer research.

Keywords: Cancer; Drug development; Drug efficacy; Drug toxicity; Immunotherapy; Organoid; Personalized medicine; Regeneration medicine.

Fig. 1

Organoid establishment from stem cells and cancer cells. Embryonic stem cells from human embryonic tissues and induced pluripotent stem cells from adult tissues firstly experience directed differentiation, generate floating spheroids, and subsequently are planted on extracellular matrix in specific culture medium to initiate organoid culture. Primary tissues from patients can be dissociated into functional units, which contain somatic stem cells. These somatic stem cells are enriched and cultured in three-dimensional medium to form organoids. Tumor cells isolated from cancer tissues can also form tumoroids in well-defined three-dimensional culture

Fig. 2

Potential applications of organoids in tumor modeling, drug development, and regeneration medicine. Organoid technology can be exploited to model human cancers (a), and gene-profiling analyses (b) of tumoroids and corresponding healthy organoids promote the identification of novel targeted therapies. Organoids can also promote the development of anti-tumor drugs, including efficacy testing (c) and toxicity testing (d). In addition, organoids can be a potential candidate in regeneration medicine for the replacement of irreversibly progressively diseased organs with healthy organoids (e). Besides, organoids can also be cryopreserved for academic studies (f)

Fig. 3

Flow charts for tumoroid establishment processes. Major steps during tumoroid establishment of gastrointestinal cancer (a), liver cancer (b), pancreatic cancer (c), breast cancer (d), bladder cancer (e), and prostate cancer (f) are shown