The Patient-Derived Cancer Organoids: Promises and Challenges as Platforms for Cancer Discovery
Abstract
:Simple Summary
Abstract
1. Introduction
2. Unmet Needs for the Model System Recapitulating Human Cancer Biology
2.1. Non-Human Model System
2.2. Patient-Derived Cancer Cell Lines
2.3. Syngeneic Mouse Models and PDXs
3. Possible Applications Using PDCOs for Cancer Research
3.1. PDCO Biobank
3.2. Drug Efficacy Study and High-Throughput Screening
3.3. Precision Cancer Medicine
4. PDCO Challenges as Cancer Biology Models
4.1. Establishment Rate of PDCOs
4.2. Requirements to Recapitulate Human Cancer Biology
4.2.1. Matrix
4.2.2. Vasculature
4.2.3. Stromal, Immune Cells
4.3. Advantages of PDCO Models
4.3.1. Media
4.3.2. Matrix
4.3.3. Vascularization
4.3.4. Immune and Stromal Cells
4.3.5. Organoids-on-a-Chip
5. Conclusions and Perspective
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Niche Factor | Supplement | Role | Functions | Ref. |
---|---|---|---|---|
WNT | WNT3a | WNT ligand | initiates the canonical Wnt/β-catenin pathway. WNT3a is required to the clonal expansion of Alveolar type 2 cells Airway organoid is not required the addition of exogenous WNT3a. | [45,117,118] |
CHIR99021 | GSK3 Inhibitor | stimulate the WNT/β-catenin signaling strong wnt signaling impairs the formation of airwary organoid | [119,120] | |
R-spondin | agonist | amplifies the WNT/β-catenin signaling. require the expansion and long-term culture of airway organoid. | [45,117,118] | |
BMP | Noggin | BMP inhibitor | increases the number of stem cells and blocks their differentiation. maintains the stemness of stem cells. | [112,117,119] |
TGF-b | SB431542 | ALK5 inhibitor | lengthen organoid growth | [119,120] |
A83-01 | ALK4/5/7 inhibitor | prevents TGF-β induced growth inhibition. | [121] | |
FGF | FGF2 | FGFR ligand | keeps the survival of organoids. produce large organoids and induce organoid branching | [118] |
FGF7 | FGFR ligand | promotes differentiation of lung stem cells toward distal lung lineages. induces organoid branching. | [118,119,120] | |
FGF10 | FGFR ligand | promotes differentiation of lung stem cells toward distal lung lineages. induces organoid branching. | [118,120] | |
EGF | EGF | EGFR ligand | drive proliferation of organoids. not essential for organoid formation, but it increases the size of alveolar organoids | [117] |
p38 MAPK | SB202190 | p38 MAPK inhibitor | to overcome organoid growth arrest protects cells from environmental stress induced apoptosis. | [45] |
Li et al. [127] | S´andor et al. [128] | Dijkstra et al. [90] | Taverna et al. [129] | Li et al. [130] | Shi et al. [131] | Sachs et al. [45] | Kim et al. [132] | Choi et al. [133] | Kim et al. [44] | Hu et al. [134] | Endo et al. [135] | ||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
WNT | WNT3A | 100 ng/mL | - | - | - | - | - | - | - | 0 or 100 ng/mL | - | - | - |
CHIR99021 | - | - | - | - | - | 250 nM | - | - | - | - | - | - | |
R-spondin | 250 ng/mL | 500 ng/mL | 10% | 500 ng/mL | 500 ng/mL | - | 500 ng/mL | 20% | 0 or 10% | - | - | - | |
BMP | Noggin | 100 ng/mL | 100 ng/mL | 10% | 100 ng/mL | 100 ng/mL | 100 ng/mL | 100 ng/mL | 100 ng/mL | 0 or 100 ng/mL | - | - | - |
TGF-b | SB431542 | - | 1 µM | - | - | 10 mM | - | 500 nM | - | - | - | - | - |
A83-01 | 500nM | 500 nM | 500 nM | 500nM | 500 nM | 500 nM | - | 500 nM | 0 or 50 ng/mL | - | 5 μM | - | |
FGF | FGF2 | 1 ng/mL | - | - | 10 ng/mL | - | - | - | - | 20 ng/mL | 20 ng/mL | - | 10 or 100 ng/mL |
FGF7 | - | 100 ng/mL | 25 ng/mL | - | 25 ng/mL | - | 25 ng/mL | 25 ng/mL | - | - | - | - | |
FGF10 | 20 ng/mL | 100 ng/mL | 100 ng/mL | 10 ng/mL | 20 ng/mL | 100 ng/mL | 100 ng/mL | 100 ng/mL | - | - | - | - | |
EGF | EGF | 50 ng/mL | - | - | 50 ng/mL | - | 50 ng/mL | - | - | 50 ng/mL | 50 ng/mL | 50 ng/mL | 10 or 100 ng/mL |
p38 MAPK | SB202190 | 10 μM | - | 1 μM | 5 μM | 10 mM | - | 500 uM | 500 nM | - | - | 3 μM | - |
ROCK | Y-27632 | - | 5 µM | 5 μM | 10 μM | 10 mM | 10 μM | 5 uM | 10 μM | 10 μM | 10 μM | 10 μM | - |
etc | 1 μM PGE2, 10 nM Gastrin 1 | 0 or 10 µM Nutlin-3a, 40 ng/mL Heregulin β-1 | 5 μM Nutlin-3a | 1 μM PGE2, 20 ng/mL HGF | - | 100 ng/mL FGF4, 100 nM SAG | - | - | - | - | 10 μM Forskolin, 3 nM Dexamethasone | 10 or 100 ng/mL NRG1, 10 or 100 ng/mL IGF1, 10 or 100 ng/mL ActivinA, 10 μg/mL transferrin | |
supplement | NA | 10 mM | 10 mM | 10 mM | - | 10 mM | - | - | 5 mM | - | - | 5 mM | - |
B27 | 1× | 1× | 1× | 1× | 1× | 1× | 1× | 1× | 1× | 1× | 2% (v/v) | - | |
N2 | 1× | - | - | 1× | - | - | - | - | 1× | 1× | 1% (v/v) | - | |
NAC | 1 mM | 1.25 mM | 1.25 mM | 4 mM | 1.25 mM | 1.25 mM | - | 1.25 mM | - | - | 1 mM | - | |
etc | - | - | - | - | - | - | - | - | - | - | - | 1× trace elements A, B, C 1× nonessential amino acids 50 μg/mL ascorbic acid | |
Base medium | Ad-DF+++ | DMEM/F12 | Ad-DF+++ | Ad-DF+++ | Ad-DF+++ | Ad-DF+++ | Ad-DF+++ | Ad-DF+++ | Ad-DF+++ | DMEM/F12 | DMEM/F12 | DMEM/F12 | |
matrix | Matrigel (ratio is not determined) | 100% Matrigel | 10 mg/mL geltrex | 100% Matrigel | 100% Matrigel | 100% matrigel | 10 mg/mL Cultrex | 100% matrigel | 66% matrigel | 66% matrigel | 100% Matrigel | 100% Matrigel | |
success rate | 71% | - | 41% | 55% | 80% | 63% (short-term) 10% (Long-term) | 88% | 83% | 80% | 56% | 79% | 80% | |
resected source | NSCLC (n = 14) | AC (n = 6) | Total (n = 59) AC (n = 46) SCC (n = 4) LCNEC (n = 2) NSCLC (n = 7) | Total (n = 11) AC (n = 10) ASC (n = 1) | AC (n = 15) | Total (n = 30) AC (n = 16) SCC (n = 14) | NSCLC (n = 16) | advanced AC (n = 100) | SCLC (n = 10) | Total (n = 36) AC (n = 23) SCC (n = 8) LCC (n = 2) SCC (n = 2) ASC (n = 1) | Total (n = 103) AC (n = 71) SCC (n = 23) SCLC (n = 4) other (n = 5) | Total (n = 125) AC (n = 82) ASC (n = 6) SCC (n = 31) LCC (n = 4) Pleomorphic (n = 2) |
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Bae, J.; Choi, Y.S.; Cho, G.; Jang, S.J. The Patient-Derived Cancer Organoids: Promises and Challenges as Platforms for Cancer Discovery. Cancers 2022, 14, 2144. https://doi.org/10.3390/cancers14092144
Bae J, Choi YS, Cho G, Jang SJ. The Patient-Derived Cancer Organoids: Promises and Challenges as Platforms for Cancer Discovery. Cancers. 2022; 14(9):2144. https://doi.org/10.3390/cancers14092144
Chicago/Turabian StyleBae, JuneSung, Yun Sik Choi, Gunsik Cho, and Se Jin Jang. 2022. "The Patient-Derived Cancer Organoids: Promises and Challenges as Platforms for Cancer Discovery" Cancers 14, no. 9: 2144. https://doi.org/10.3390/cancers14092144