Integration of Genomic Profiling and Organoid Development in Precision Oncology
Abstract
:1. Introduction
2. Single-Cell Sequencing-Matched Cancer Treatment
2.1. Ovarian Cancer
2.2. Breast Cancer
3. Advanced Genome Profiling Combined with the Use of Cancer Organoids
3.1. Ovarian Cancer
3.2. Breast Cancer
4. Organoids on a Chip
5. Conclusions
Application | Functional Study | Reference | |
---|---|---|---|
Ovarian cancer | Basic research | Transcriptome expression profiles of individual cells; intratumoral heterogeneity within ovarian cancer and ascites (fibroblast, T cell, B cell, macrophages, dendritic cells) | [40,41,42,43,110] |
Druggable target, translational research | Individual gene expression of immune cells in HGSOC; contribution of JAK/STAT signaling in inflammatory programming; drug screening with cucurbitacin I in vitro and in vivo; identification of grade and origin specific cell populations | [44,47,48] | |
Cancer stem cell | Comparison of gene expression profiles between ovarian cancer and embryonic tissues; cell population expressing PEG10 modulates ovarian cancer stemness and drug resistance | [49] | |
Drug resistance | Identification of chemo-resistant cell population in HGSOC; the cells express CD44, MYD88, and ALDH1 | [53] | |
Omentum (ovarian cancer) | Druggable target | High T cell infiltration in the omentum in ovarian cancer patients; increase of antitumor response; providing therapeutic targeting | [52] |
Breast cancer | Basic research | Single-cell transcriptome profiling of individual cells; clonal evolution; genomic evolution in TNBC; characterization of heterogeneous tumor cells with stromal and immune cells (T cell, B cell, macrophages, CAFs); intratumoral heterogeneity within breast cancer | [64,65,66,67,68] |
Advanced scRNA-seq research | Nanogrid single-nuclear RNA sequencing; heterogenous phenotypic profiles of breast cancer related to angiogenesis, cell proliferation, and cancer stemness | [69] | |
Translational research | scRNA-seq analysis using 40 TNBC patients with neoadjuvant anti-PD1; CCR2+ or MMP9+ macrophage and dendritic cells increased T cell expansion; providing therapeutic targeting for synergistic effect with anti-PD1 | [80] | |
Cancer stem cell, Drug resistance Translational research | CAF-induced Hedgehog ligand promotes chemo-resistant and cancer stem cell population in TNBC; chemotherapy-induced transcriptional reprogramming of resistant signatures; smoothened inhibitors (SMOi) sensitize tumors with docetaxel in vivo; providing a therapeutic target in TNBC | [82,83] |
Source | Development Efficiency | Features and Use | Reference | |
---|---|---|---|---|
Ovarian cancer | 56 organoid lines derived from 32 patients | Medium (~65%) | Maintaining CNVs, recurrent mutations and tumor heterogeneity; long-term expansion; providing drug screening platform; in vivo tumorigenicity; sensitive to platinum-based therapy | [91] |
33 organoid lines derived from 22 HGSOC patients | High (80–90%) | Maintaining DNA repair gene mutational status in HGSOC; providing DNA repair profiling and a rapid functional platform for therapeutic sensitivity testing | [92] | |
14 organoid lines derived from 3 HGSOC, 1 clear cell, 3endometrioid patients | High (~80%) | Replicating the mutational landscape of the primary tumors; maintaining similar CNVs and BRCA1 pathogenic variant; sensitivity to PARP inhibitor, olaparib, and platinum drugs | [93] | |
14 organoid lines derived from 21 gynecologic tumors | High (~95%) | Retaining features of histology and mutations of original tumors; retention of intra-tumoral heterogeneity; only 1 organoid model has in vivo tumorigenicity; drug response assay using organoid-derived spheroids | [90] | |
Breast cancer | >100 organoid lines derived from >150 patients | High (>80%) | Matching the histopathology, hormone receptor status, and HER2 status of the parental tumor; generic variations retained after long-term expansion; providing in vitro drug screens; sensitive to drugs (e.g., afatinib and pictilisib) blocking the HER signaling pathway | [94] |
45 biobanked breast organoid cultures | Medium (55–70%) in most subtypes; Low (~40%) in TNBC | Organoids covering all major breast cancer subtypes; providing genetically edited normal breast organoids using CRISPR–Cas9; providing in vitro and in vivo drug screening platform | [97] | |
99 organoids derived from 132 samples | Medium (~75%) | Recapitulating the histopathologic and genetic characteristics of parental tumors; in vitro drug sensitivity screening; sensitive to microtubule-targeting drugs | [98] |
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Yoon, H.; Lee, S. Integration of Genomic Profiling and Organoid Development in Precision Oncology. Int. J. Mol. Sci. 2022, 23, 216. https://doi.org/10.3390/ijms23010216
Yoon H, Lee S. Integration of Genomic Profiling and Organoid Development in Precision Oncology. International Journal of Molecular Sciences. 2022; 23(1):216. https://doi.org/10.3390/ijms23010216
Chicago/Turabian StyleYoon, Hyunho, and Sanghoon Lee. 2022. "Integration of Genomic Profiling and Organoid Development in Precision Oncology" International Journal of Molecular Sciences 23, no. 1: 216. https://doi.org/10.3390/ijms23010216