Emerging organoid models: leaping forward in cancer research

Abstract

Cancer heterogeneity is regarded as the main reason for the failure of conventional cancer therapy. The ability to reconstruct intra- and interpatient heterogeneity in cancer models is crucial for understanding cancer biology as well as for developing personalized anti-cancer therapy. Cancer organoids represent an emerging approach for creating patient-derived in vitro cancer models that closely recapitulate the pathophysiological features of natural tumorigenesis and metastasis. Meanwhile, cancer organoids have recently been utilized in the discovery of personalized anti-cancer therapy and prognostic biomarkers. Further, the synergistic combination of cancer organoids with organ-on-a-chip and 3D bioprinting presents a new avenue in the development of more sophisticated and optimized model systems to recapitulate complex cancer-stroma or multiorgan metastasis. Here, we summarize the recent advances in cancer organoids from a perspective of the in vitro emulation of natural cancer evolution and the applications in personalized cancer theranostics. We also discuss the challenges and trends in reconstructing more comprehensive cancer models for basic and clinical cancer research.

Keywords: 3D Bioprinting; Cancer heterogeneity; Cancer organoids; In vitro model system; Organ-on-a-chip; Patient-derived tumor organoids; Personalized anti-cancer therapy.

Fig. 1

Cancer organoids can be derived from patients with diverse cancer grades and subtypes. Patient-derived organoids can possess patient-specific genetic and epigenetic contexts for preclinical cancer research and theranostics. Meanwhile, normal organoids can be used to model cancer evolution after the introduction of oncogenic mutations. By using the time-lapse microscopic imaging, tumor cell behaviors can be monitored in real-time. Similar to cell lines, cancer organoid lines can be expanded and cryopreserved to establish a living organoid biobank

Fig. 2

Patient-derived cancer organoids can be derived from surgically resected/biopsied tissues and circulating tumor cells. Additionally, using the gene-editing technique, normal organoids can be mutated into tumor organoids

Fig. 3

a A vascularized organ-on-a-chip model was utilized to analyze BC cell invasion and metastasis through a microvascular network. b A multi-organ-on-a-chip system was composed of a “primary site” and three “main sites of metastatic”. This microfluidic system was used to model lung cancer metastasis to distant organs, which provided an experimental platform to analyze cell-microenvironment interactions in organ-specific metastasis. c Schematic diagram of the 3D bioprinting technology for organ-on-a-chip models. d An extrusion-based bioprinting platform that interrogates the paracrine loop between BC cells and macrophages in different geometric arrangement. An extrusion-based 3D bioprinting technique for constructing breast cancer metastasis model. e Fabrication of the 3D HeLa/hydrogel spheroids by 3D printing