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Table 1 Brief description of studies done using various omics techniques and 3-D in vitro tumor models

From: Integration of pan-omics technologies and three-dimensional in vitro tumor models: an approach toward drug discovery and precision medicine

Sl. No

Type of omics used

Method adopted

Type of cancer studied

Purpose of the study

References

1.

Genomics

WGS

Breast cancer

Validation of PDO model using patient data

[125]

2.

WGS

Gastrointestinal cancer

Validation of PDO model using patient data

[126]

3.

WGS

Colorectal cancer

Validation of PDO model using patient data

[127]

4.

WGS

Esophageal cancer

Validation of PDO model using patient data

[128]

5.

WGS

Gastric cancer

Human and mouse gastric cancer organoids to check different drug targets

[129]

6.

NGS

Ovarian tumor & endometrial tumor

Validation of PDO model using patient data

[130]

7.

WGS

Gastroenteropancreatic (GEP) neuroendocrine neoplasm

Validation of PDO model for identification of new therapeutic targets

[37]

8.

WGS

Pancreatic cancer

Validation of 3-D models for identification of genomic markers contributing towards drug sensitivity

[39]

9.

WGS

Kidney cancer

Validation of PDO model based on pediatric kidney cancer patients

[38]

10.

WGS

Colon cancer, Breast cancer

PDO based model for studying the changes in mutational landscape of tumor when exposed to fluoropyrimidines

[131]

11.

WGS

Ovarian cancer

PDO based models to understand the inter- and intra-patient heterogeneity to drug response

[132]

12.

WES

Prostate cancer

PDO model to understand association of EZH2 driven molecular changes with cancer progression

[122]

13.

WES

Prostate cancer

Recapitulation of molecular diversity of the various subtypes of prostate cancer and validation of PDO Model

[36]

14.

WES

Gastric cancer

Establishment of primary gastric cancer organoid biobank & molecular profiling

[133]

15.

WES

Colorectal cancer

Biobank establishment, gene-drug association, validation using PDO model and 3-D model

[10, 35, 134]

16.

WES

Brain cancer

PDO models of pediatric high-grade gliomas to understand the role of hypoxia in cancer progression

[135]

17.

CRISPR-Cas9 screening with NGS

Colon cancer

PDO model to screen patient-specific functional genomics

[41]

18.

Transcriptomics

Microarray

Breast cancer

Studied the gene expression profile affecting the drug response in 3-D compared to 2-D model

[23, 24]

19.

RNA-Seq

Colorectal cancer

Transcriptomic and chromatin profiling for personalized drug targets to overcome chemoresistance

[49]

20.

RNA-Seq

Endometrial cancer

PDO based Biobank development which recapitulated the lesions from all clinical stages and can be used for drug screening purposes

[50]

21.

RNA-Seq

Breast cancer

PDO model validation using patient data

[125]

22.

RNA-Seq

Pancreatic cancer

PDO & PDX derived organoid model for understanding genomic and histopathological changes along with drug testing

[136]

23.

RNA-Seq

Colorectal cancer

Colonic organoids from induced pluripotent stem cells used in disease modelling and drug discovery for colorectal disease

[137]

24.

RNA-Seq

Bladder cancer

Validation of PDO model using patient data

[58, 138]

25.

RNA-Seq

Liver cancer

Micro-scaffold-based model to enumerate relationship between EMT status and hepatic functions

[139]

26.

RNA-Seq

Brain cancer

PDOs developed via CRISPR-Cas9-mediated mutagenesis for drug testing

[140]

27.

RNA-Seq

Colorectal cancer

Patient-derived organotypic tumor spheroids in 3-D microfluidic culture to screen the response of immune check point blockade therapy

[93]

28.

RNA-Seq

Colorectal cancer

Model validation of 2-D patient derived cancer cells, 3-D air-liquid interface based organoid culture and xenograft for identification of potential drug targets

[141]

29.

RNA-Seq

Colorectal cancer

PDOs for therapeutic drug screening

[54]

30.

RNA-Seq

Lung cancer

Development of PDO models to recapitulate the tumor heterogeneity and to identify the targets against Wnt signalling

[60]

31.

RNA-Seq

Pancreatic cancer

PDO based models to identify transcriptomic groups involved in invasion

[64]

32.

RNA-Seq

Brain tumor

Pediatric patients derived 3-D culture model to study the microenvironment induced gene expression changes

[142]

33.

GeneChip™ Human Transcriptome Array

Metastatic colorectal cancer

Pharmacogenomic profiling for PDO models to check the drug sensitivity

[59]

34.

Single‐cell RNA-Seq

Metastatic colorectal cancer

PDO formed to recapitulate the tumor heterogeneity and further used to study the drug response

[52]

35.

Single‐cell RNA-Seq

Metastatic renal cell carcinoma

3-D model for combinatorial drug therapy

[61]

36.

Single‐cell RNA-Seq

Glioblastoma

Laboratory engineered glioblastoma organoid models to recapitulate genetic heterogeneity and identification of various drug targets

[65]

37.

Single‐cell RNA-Seq

Multi organ tumors

PDO based models to recapitulate tumor immune microenvironment for personalized therapeutic applications

[143]

38.

miRNA Microarrays

Colorectal adenoma and colorectal cancer

PDO utilised to understand the miRNA signature patterns in colorectal adenoma and colorectal cancer

[75]

39.

Proteomics

Mass spectrometry

Pancreatic cancer

Extracellular vesicle protein profiling to investigate tumorigenesis

[81]

40.

Mass spectrometry

Colorectal cancer

Organoid based model to show the effect of SMAD4 inactivation on metastasis

[83]

41.

Mass spectrometry

Pancreatic cancer

Murine and human derived organoids to investigate the pancreatic cancer pathogenesis

[144]

42.

Mass spectrometry

Colorectal cancer

Organoids from healthy donor and cancer patients subjected to proteomic analysis to understand the patient-specific protein signatures

[145]

43.

DigiWest multiplex protein profiling

Colorectal cancer

PDO based model for studying tumor heterogeneity and prediction of therapy response

[146]

44.

Single-cell mass cytometry (CyTOF®)

Breast cancer

Primary breast organoids to preserve complex epithelial lineage

[147]

45.

LC-MS/MS analysis

Brain cancer

Drug screening platform using patient derived neurospheres/3-D culture

[85, 148]

46.

LC–MS/MS -SWATH

Colorectal cancer

PDO based model to integrate the drug sensitivity with proteomics for prediction of better therapeutic response

[84]

47.

LC-MS/MS analysis

Colon cancer

Quantitative proteomic and phosphoproteomic analysis of 3-D spheroids

[90]

48.

Reverse phase protein microarray

Colon cancer

PDO based model to study altered molecular pathway involved in tumorigenesis

[33]

49.

Reverse phase protein microarray

Multiple Cancers

Compared 121 different phosphorylated and non-phosphorylated proteins between 2-D and 3-D cell cultured models under the influence of hypoxia

[89]

50.

Protein Array

Colorectal cancer

PDO based models to identify the role of MIR21 dysregulation, JAM-A silencing and signalling pathways involved in tumorigenesis

[149]

51.

Milliplex® MAP Human Cytokine/Chemokine Panel

Pancreatic cancer

To study the effect of tumor cells and fibroblast on monocytes in a 3-D co-culture model

[92]

52.

Metabolomics and lipidomics

1H-NMR Spectroscopy

Brain cancer

To validate patient-derived model in hypoxic microenvironment

[135]

53.

Mass spectrometry and Raman chemical imaging

Breast cancer

Cell line-based spheroid model to map lipid distribution during disease progression

[115]

54.

Mass spectrometry

Breast cancer

Spheroid based model to study the effect of bisphenol- S on tumor progression

[98]

55.

Mass spectrometry

Prostate and breast cancer

Spheroid models to evaluate the alterations in intracellular lipid concentrations when treated with metabolic enzyme inhibitors

[113]

56.

LC-QTOF-MS

Colorectal cancer

PDO based models used for metabolomic and lipidomic profiling when treated with 5-fluorouracil

[108]

57.

Optical metabolic Imaging

Breast cancer and pancreatic cancer

PDO based models to analyse the optical metabolic imaging of cellular heterogeneity as a predictor of clinical treatment response

[150]

58.

LCMS

Breast cancer

PDO based model to describe the metabolomic landscape of TNBC patients

[107]

59.

HPLC-MS/MS

Colorectal cancer

Understanding the mechanism of curcumin in PDO based model

[151]

60.

Organ on chip platform with electrochemical microsensors

Breast cancer

Patient derived breast cancer stem cell based organoid model for in situ metabolite monitoring and drug screening

[152]

61.

Mass spectrometry

Ovarian cancer

PDO based model for drug testing and to evaluate the role of lipid metabolic activities in cancer progression

[112]

62.

UHPLC

Colorectal cancer

PDO based models to identify the role of drug sensitizing activity of spirulina polysaccharides in 5 fluorouracil resistant CRC organoids

[153]

63.

UPLC-MS

Multiple tumor cells

Chip based 3-D co-culture model to evaluate metabolism induced anticancer activity

[96]

64.

MALDI Mass Spectrometry Imaging

Colorectal cancer

PDO based model to examine drug and its metabolite distribution

[102]

65.

GCxGC-MS Analysis

Ovarian cancer

To evaluate the difference in intracellular and extracellular metabolite profile amongst ovarian cancer cell and spheroid derived ovarian cancer stem cells

[105]

66.

LCMS

Breast cancer

To understand the changes in lipidome during breast cancer metastasis

[116]

67.

Epigenomics

DNA methylation profiling

Kidney cancer

Validation of PDO model based on pediatric kidney cancer patients

[38]

68.

Enhanced reduced representation bisulfite sequencing

Prostate cancer

PDO based models used to understand the role of epigenetic modifier EZH2 in cancer progression

[122]

69.

ATAC Seq

Pancreatic cancer

PDO based model to study chromatin accessibility associated with drug sensitivity

[154]

70.

Whole-genome bisulfite sequencing

Colorectal cancer

PDO based model used to evaluate the transcriptomic and epigenetic landscape with respect to the culture conditions

[155]

71.

Methylation epic bead ChIP microarrays

Colorectal cancer

PDO based model used to prove the anti-metastatic activity of ginseng by inhibiting the expression of DNA methyltransferases

[156]

72.

ChIP Seq

Prostate cancer

PDX/PDO models to understand the lineage plasticity and epigenetic reprogramming induced by N-Myc

[120]

73.

Methylation array analysis

Osteosarcoma

Comparing 3-D bio-printed model with other tumor models for changes in cell cycle, metabolomics and epigenetic regulation

[121]

74.

m6A methylated RNA immunoprecipitation sequencing

Colorectal cancer

The tumorigenic effect of YTHDF1-m6A-ARHGEF2 axis on disease progression studied on organoids and mice models

[123]

  1. WGS whole genome sequencing, WES whole exome sequencing, PDOs patient-derived organoids, PDX patient-derived xenografts, CRC colorectal cancer, LC-MS/MS liquid chromatography-tandem mass spectrometry, MIR21 MicroRNA-21, JAM-A junctional adhesion molecule-A, 1H-NMR proton nuclear magnetic resonance, LC-QTOF-MS liquid chromatography quadrupole time-of-flight mass spectrometry, HPLC-MS/MS high-performance liquid chromatography mass spectrometry, NGS next generation sequencing, RNA-Seq RNA sequencing, UHPLC Ultra high-performance liquid chromatography, UPLC-MS Ultra-performance liquid chromatography coupled with mass spectrometry, MALDI MSI Matrix-assisted laser desorption/ionization – Mass spectrometry imaging, GCxGC-MS two-dimensional gas chromatography coupled to mass spectrometry, ChIP- chromatin immunoprecipitation, CyTOF® cytometry by Time-Of-Flight