Table 3 Research applications of urological cancer organoids
From: Urological cancer organoids, patients' avatars for precision medicine: past, present and future
Year | Author | Application | Model | Mainly findings | Refs |
|---|---|---|---|---|---|
2014 | Gao et al. | Disease modeling | PCO | Human prostate cancer organoids have been established for the first time and these organoids can reproduce the characteristic copy number and mutation profiles commonly found in prostate cancer | [40] |
2016 | Drost et al. | Disease modeling | PCO | They first cultured organoids derived from human metastatic prostate cancer biopsies and describe a specific culture protocol | [21] |
2018 | Park et al. | Disease modeling | NEPC organoid | Generation of NEPC organoids from benign prostate epithelial cells | [41] |
2021 | Servant et al. | Disease modeling | PCO | Furthermore, developed a biobank consisting of PCOs derived from 81 patients with primary and metastatic prostate cancer. A significant correlation was observed between the percentage of tumour cancers in the parental sample and organoid growth, implying that tumour purity could be a predictive factor for organoid growth | [42] |
2016 | Justin et al. | Disease modeling | BCO | They established 4 organoid lines derived from cancer specimens and found that organoids exhibited mutations that were highly concordant with original cancer samples | [51] |
2018 | Lee et al. | Disease modeling | BCO | Bladder cancer organoids harboring ERBB2 mutations and FGFR3-TACC3 fusions were established and their mutational, molecular and histopathological features were highly consistent with original cancers | [52] |
2019 | Mullenders et al. | Disease modeling | BCO | They created a variety of BCOs including basal and luminal subtypes. Moreover, all mouse and most human BCOs contained cells that stained positive for keratin 5 and CD44, which are two potential cancer stem cell markers | [22] |
2015 | Takasato et al. | Disease modeling | Kidney organoid | They established iPSC-derived kidney organoids | [67] |
2015 | Pan et al. | Disease modeling | RCO | They established renal cancer organoids from 786-O cell lines. These organoids expressed ccRCC characteristic gene CXCR4 and selective adhesion molecules, angiogenic factors and osteolytic factors related to bone metastasis | [68] |
2015 | Batchelder et al. | Disease modeling | RCO | 20 renal cancer organoids were established from 25 ccRCC samples | [32] |
2016 | Drost et al. | Medium optimization | PCO | A fully defined serum-free medium for prostate cancer organoid was developed in which organoids contain pluripotent progenitor cells; can be cultured long-term; and contain the androgen receptor signaling pathway | [21] |
2022 | Cheaito et al. | Medium optimization | PCO | They simplified the regular 12-factor medium into a 5-factor medium. The 5-factor medium was found to increase the number and size of prostate cancer organoids, but prolonged culture time. The addition of R-spondin1 can significantly shorten the culture time | [46] |
2019 | Mullenders et al. | Medium optimization | BCO | A stable human bladder cancer organoid culture medium was developed and FGF7 and FGF10 were observed to stimulate the proliferation of human bladder cancer organoids | [22] |
2018 | Yoshida et al. | Medium optimization | BCO | The addition of heregulin and CHIR99021 to the medium promoted the growth of bladder cancer organoids | [15] |
2020 | Fendler et al. | Medium optimization | RCO | Amphotericin B, and heparin are added to the culture medium of ccRCC organoids and are widely used | [23] |
2020 | Elbadawy et al. | Drug screening | PCO | They demonstrate that PTEN deletion enhances resistance to next-generation anti-androgens, and that prostate cancers with double deletions of p53 and PTEN will be completely resistant to new-generation anti-androgens | [72] |
2019 | Chakraborty et al. | Drug screening | PCO | It was found that co-deletion of BRCA2 and RB1 induces EMT and is associated with cancer aggressiveness and progression; the PARP inhibitor olaparib inhibits the growth of mCRPC-derived organoids and promotes cancer cell apoptosis | [74] |
2018 | Lee et al. | Drug screening | BCO | Different organoids showed different responses to the MEK inhibitor trametinib and the ERK inhibitor SCH772984. Muscle-invasive carcinomas and tumors that recur after treatment failure showed greater drug resistance | [52] |
2020 | Kong et al. | Drug screening | BCO | They found the "amino acid synthesis and interconversion" pathway showed high predictive performance by network-based machine learning | [75] |
2019 | Grassi et al. | Drug screening | RCO | They demonstrated that ccRCC organoids were sensitive to SU11274 and foretinib and had reduced pAKT and pERK gene expression. Furthermore, forratinib sustained apoptosis in ccRCC organoids | [33] |
2019 | Grassi et al. | Nephrotoxicity testing | Renal organoid | They found that renal cell subtypes in which cleaved-Caspase3 co-expressed with LTL and WT1 antigens were sensitive to cisplatin. But only the tubular cells were damaged | [33] |
2015 | Åkerfelt et al. | TME | PCO | Using a real-time live-cell measurement platform, they observed that CAFs promote cancer organoid growth and invasion. And found that FAK inhibitors Y11 and PF-573228 selectively disrupted cancer-CAFs interactions, inhibited caner growth and invasion, and had no apparent cytotoxicity [46] | [83] |
2021 | Dhimoleaet et al. | TME | PCO | Co-culturing prostate cancer organoids with BMSCs and found that IL-6 secreted by BMSCs induced hormone-independent growth of prostate cancer organoids by activating the JAK/STAT signaling pathway and the model was less sensitive to enzalutamide | [84] |
2018 | Neal et al. | TME | RCO | They used an ALI method propagated PDOs from 100 human ccRCC biopsies or syngeneic immunocompetent mice as cancer epithelia with native embedded immune cells. The association in vivo between native TILs and cancer cells is preserved. They demonstrated that PDOs accurately preserved the original cancer TCR profile by 10 × Chromium single-cell sequencing. Both human and mouse cancer organoid TILs functionally exhibit activation, expansion and cytotoxicity responses to PD-1/PD-L1 checkpoint blockade | [85] |
2014 | Chua et al. | Cancer origin | PCO | They established mouse prostate cancer organoids using a prostate cancer luminal cell line and showed through lineage tracing that luminal cells facilitate organoid formation and generate basal cells in culture, suggesting progenitor properties of luminal cells | [88] |
2016 | Liu et al. | Cancer origin | PCO | Low CD38 expression can be used as a biomarker to identify luminal cells of prostate cancer | [90] |
2016 | Park et al. | Cancer origin | PCO | Both basal and luminal cells are thought to be progenitors of prostate cancer. Both basal and luminal cells can respond to the same oncogenic lesions to initiate tumorigenesis, but with different tumor phenotypes | [91] |
2014 | Choi et al. | Cancer origin | BCO | Basal-type bladder cancer was found to be more aggressive, metastatic, and less survival than the luminal type, and was more sensitive to cisplatin-based chemotherapy | |
2016 | Ohishi et al. | Cancer origin | BCO | Single cells from Shh-expressing cell derived organoids were able to self-renew and generating new organoids in subsequent cultures, suggesting that Shh-expressing basal urothelial cell populations include pluripotent stem cells | [54] |
2015 | Mout et al. | Precision treatment | PCO | Pioneering use of DLA to increase CTCs in patients with metastatic prostate cancer. This method provides a rich source for culturing organoids, enabling liquid biopsies | [96] |
2017 | Usui et al. | Precision treatment | Dog PCO | For the first time, they established urine cancer stem cells derived PCOs from dogs with prostate cancer. They observed expression of the epithelial cell marker E-cadherin in the organoids by immunofluorescence staining | [99] |
2019 | Elbadawy et al. | Precision treatment | Dog BCO | They generated dog bladder cancer organoids using urine samples. They found that the expression levels of MMP28, CTSE, CNN3, TFPI2, COL17A1 and AGPAT4 were specifically upregulated in dog BCOs | [100] |
2020 | Sun et al. | Precision treatment | RCO | They used 10% kECM to establish human USCs derived kidney organoids. And they demonstrated that USCs-derived kidney organoids were similar to HKCs derived organoids in morphology, histology and specific gene expression | [103] |
2018 | Wu et al. | Single-cell sequencing | Kidney organoid | Researchers compared single-cell transcriptomics of 83,130 cells from 65 kidney organoids with fetal and adult kidney cells by single-cell RNA sequencing. The results showed the organoid-derived cell types were immature with 10%-20% of the cells being non-renal cells and mostly neurons | [114] |
2020 | Calandrini et al. | Single-cell sequencing | Kidney tumor organoids | They established the first organoid biobank for paediatric cancers which included 54 kidney tumor organoids and matched normal kidney organoids. Using single-cell RNA sequencing and high-resolution 3D imaging, they demonstrated that Wilms tumor-derived organoids are composed of multiple distinct cell types including epithelial, stromal and blastocyst-like cells | [115] |
2020 | Fendler et al. | Single-cell sequencing | RCO | They used single-cell sequencing to determine the degree of heterogeneity within the kidney CSCs population. This yielded three subpopulations, two of which exhibited high expression of markers known to be associated with stem cells and kidney development | [23] |