Table 2 Organoids models for organs and cancers of female reproductive tract.

From: Organoid modeling meets cancers of female reproductive tract

Organoid model types

Organoid sources

Numbers of organoid lines

Hotspot mutations

Model validation method

Applications

Ref.

Cervix uterus

SqCa

Patient tumor tissue

11

TP53, ARID1B, CDKN2A, ELF3, FAT1, BRCA1/2, ATM, FANCA

Histological analysis, phenotype markers, gene expression patterns, genetic mutations, viral transcriptome

Drug screening, xenograft, viral infection model, HPV infection study

[50]

AdCa

Patient tumor tissue

1

FBXW7, CASP8, NOTCH3, PDGFRB, TSC2, EPHA2, EPHA5

Invasive SqCa, AdCa, LCNEC, villoglandular AdCa, SCNEC

Patient tumor tissue

17

KRAS, TP53, KMT2C, PRSS1

Histological analysis, diagnostic marker, copy number variation

High-throughput drug screening, radiotherapy response prediction

[59]

HSIL

Patient HSIL tissue

22

MUC16, PRUNE2

Histological analysis, phenotype markers, karyotype identification, subcellular structure, HPV testing, gene expression patterns, genetic mutations

Drug screening, xenograft, co-culture with PBMC

[63]

SqCa

Patient tumor tissue

15

HLA-B, ERBB3, ERBB2, NDC80, KLF6, EPS8, WASF2, MARK2, PIK3R4, TRIP12, CDKN2AIP, ISG15, FLT1, UBE3A, SERPINB2, RBBP8

SqCa, AdCa

Patient tumor tissue

67

PIK3CA, EP300, FBXW7, PTEN, ARID1A, TTN

Pathological analysis, HPV testing, phenotype markers, gene expression patterns, genetic mutations

Radiotherapy and combined platinum sensitivity testing, paired TILs killing assay, xenograft

[69]

CCC

Patient tumor tissue

1

PIK3C2B, MLH1, FLT1, SMARCA4, TFE3

Pathological analysis, genomic DNA analysis

Drug screening

[65]

SCCC

Patient tumor tissue

1

AHNAK, CNOT1, KIAA1551, KRAS, MAP2K3, SON, XIRP2, ATP2B3

Histological analysis, phenotype markers, genetic mutations, HPV18 integration sites

KRAS pathway inhibitor testing, xenograft

[67]

Healthy ectocervix

Human cervix tissue

N/A

N/A

Histological analysis, phenotype markers, transcriptomic analysis, live-cell imaging, HPV testing

HPV and Chlamydia trachomatis infection study, co-culture with γδ T cells

[53, 54, 64]

Endometrium

EC

Patient tumor tissue

N/A

FBXW7, ARID1A, PTEN, CTCF, PIK3CA, TP53, POLE, FAT1, CTNNB1

Mutational landscape analysis

Tumor heterogeneity study, drug screening, xenograft

[9]

Lentiviral transduction, searching therapeutic targets

[87]

EC

Patient tumor tissue

15

N/A

Histological analysis, phenotype markers

Drug screening, response prediction to estrogen and progesterone

[82]

EC

Patient tumor tissue

3

PTEN, ZNF286A, ARAID1A, PIK3CA, FGF

Histological analysis, phenotype markers, genetic mutations

Treated by cancer-associated fibroblasts culture supernatant

[90]

EC

Patient tumor tissue

11

N/A

Pathological analysis

Drug testing and mechanism research

[83]

EC

Patient tumor tissue

N/A

N/A

Phenotype markers

Drug testing and mechanism research

[80]

EC

Patient tumor tissue

2

N/A

Phenotype markers

Drug sensitivity testing

[84]

EC, serous, CCC, mixed serous and EC

Patient tumor tissue or g ascites fluid

22

N/A

N/A

Drug screening

[81]

EMC

Patient tumor tissue

5

PTEN, PIK3CA, ARID1A, CHEK2

Pathological analysis, genetic mutations

Tumorigenicity study, drug screening, xenograft

[24]

Ovary

HGSC, LGSC, CCC

Patient tumor tissue or g ascites fluid

21

N/A

N/A

Drug screening

[81]

BBT, HGSC, EMC, SBT, MC

Patient tumor tissue

9

NF1, TP53, PKHD1, DST

Pathological analysis, genetic mutations

Tumorigenicity study, drug screening, xenograft

[24]

HGSC, EMC, MBT, CCC

Patient tumor tissue

18

BRCA1, BRCA2, MLH1, PIK3CA, TP53, ARID1A, MSH2

Histological analysis, phenotype markers, genetic mutations, copy number variations

Drug screening

[121]

HGSC

Patient tumor tissue

6

TP53, FANCC, NOTCH2, BRCA1, BRIP1, RAD21, ERCC4, MSH3, ABL1, MGMT

Histological analysis, gene expression patterns, genetic mutations

Drug sensitivity testing

[123]

HGSC

Patient tumor tissue

6

ABL1, AKT2, ALK, ALOX12B, CHEK2, CSF3R, DICER1, EP300, ERCC4, FAT1

Histological analysis, phenotype markers, genetic mutations,

Drug sensitivity testing, potential target searching

[125]

LGSC

Patient tumor tissue

1

CHEK2, AKT1, IRS2, MSH3, MUTYH, NOTCH3, MLL2/KMT2D

Genetic mutations

Drug sensitivity testing

[97]

MBT, SBT, MC, LGSC, CCC, EMC, HGSC

Patient tumor tissue

56

KRAS, BRAF, TP53, MYC, CCNE1, RB1, PTEN, CDKN2A/B

Histological analysis, phenotype markers, genomic landscape

Genetic manipulation, drug screening, xenograft, drug sensitivity testing

[39]

HGSC, LGSC, HG, SBT, MBT, MC, EMC, CCC

Patient tumor tissue

36

N/A

Histological analysis, genomic features

Drug screening, tumor heterogeneity study

[41]

HGSC, high-grade mixed type carcinoma, CS, HGPC

Patient tumor tissue

4

N/A

Histological analysis

High-throughput drug screening, xenograft

[131]

HGSC

Frozen tissue from patient tumor and ascites drainage

10

CCNE1, KRAS, MYC, MECOM, RB1, CSMD3, CDK12, KMT2B, KMT2C, CCNA2

Histological analysis, phenotype markers, genomic landscape, genetic mutations, transcriptomic features

Drug sensitivity testing

[134]

HGSC

Patient tumor tissue

13

N/A

Immune cell type analysis

Co-culture with immune cells, immune checkpoint blockade testing and mechanism research

[127]

HGSC

Patient tumor tissue

33

BRCA1, BRCA2, TP53

Histological analysis, phenotype markers, genetic mutations

Drug screening, DNA repair profiling and therapeutic sensitivity testing

[119]

Fallopian tube

Early-stage carcinogenesis

iPSC

3

BRCA1

Histological analysis, differentiation markers, tumor markers, precancerous molecular properties, genetic mutations

Neoplastic conversion testing, xenograft, PARPi effect testing

[18]

  1. This table lists the female reproductive tumor organoids that have been reported in the literature and the organoid models that can be used to mimic tumors by infection or gene editing. We selected organoids derived from human stem cells, including as many valuable studies as possible. Studies that only attempted organoid construction without sufficient characterization, representational validation, and application research are not included in this table. For the gene mutation column, if the number of mutated genes mentioned in the references is too large, the top 10 mutated genes are prioritized for display.
  2. AdCa cervical adenocarcinoma, SqCa cervical squamous carcinoma, LCNEC large cell neuroendocrine carcinoma, SCNEC small cell neuroendocrine carcinoma, HSIL high-grade squamous intraepithelial lesions, SCCC small cell carcinoma of the uterine cervix, EC endometrial cancer, EMC endometrioid carcinoma, CCC clear cell carcinoma, BBT borderline Brenner tumor, HGSC high-grade serous carcinoma, MB malignant Brenner tumor, MBT mucinous borderline tumors, SBT serous borderline tumor, MC mucinous carcinoma, LGSC low-grade serous carcinoma, HG high-grade adenocarcinoma, CS carcinosarcoma, HGPC high-grade peritoneal carcinoma.