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Table 1 The establishment of GIC PDO living biobanks

From: The pivotal application of patient-derived organoid biobanks for personalized treatment of gastrointestinal cancers

Cancer type

Sample source

No.

Niche factor supplements

Success rate

Key findings

Ref

CRC

Surgery

20

Wnt, Noggin, R-Spondin, EGF, Gastrin, A83–01, SB202190, PGE2

81%

The features of genetic changes in CRC PDOs largely resembles the mutational analyses of CRC tissues.

[22]

CRC

NM

55

Wnt-3A, Noggin, R-spondin-1, EGF, Gastrin I, A83–01, SB202190

100%

CRC PDOs of various pathological types have been established. The histopathological grading and differentiation of CRC PDOs were nearly the same as those of their parental tumors in vitro and in vivo.

[23]

CRC

Biopsy and surgery

35

Wnt-3A, Noggin, R-spondin-1, EGF, Gastrin, A83–01, SB202190

60%

PDXs appear closer to the CRC molecular groups than PDOs. PDOs has less complex molecular subpopulations than PDXs due to their loss of matrix and higher expression of xenobiotic and fatty acid processes related genes.

[26]

CRC

NM

7

Wnt, R-Spondin, Noggin, EGF, Gastrin, A83–01, SB202190, PGE2

NM

The individualized patient-specific genomic and proteomic profiles of CRC PDOs may help the disease diagnosis

[27]

CRC

NM

91

Wnt-3A, Noggin, R-spondin-1, EGF, Gastrin, A83–01, SB202190

NM

The therapeutic responses and inhibitor effects on the oncogene related signal pathways to the CRC PDOs were widely variable.

[28]

mCRC

Biopsy

14

Noggin, R-Spondin, EGF, Gastrin, A83–01, SB202190, PGE2

71%

Nearly 90% of somatic mutations are shared between PDOs and matched tumors. None of the mutations that were found in either CRC tissues or CRC PDOs were genes amenable for drug targeting or in tumor driver genes.

[29]

mCRC

Surgery

3

Noggin, EGF, Gastrin, A83–01, SB202190

NM

To test the efficacy of PARP inhibitors in mCRC patients who carry HR deficient tumors and have experienced tumor shrinkage upon induction of FOLFOX-chemotherapy.

[30]

mCRC

Biopsy

40

Wnt-3A, Noggin, R-spondin-1, EGF, Gastrin, A83–01, SB202190

63%

CRC PDOs can be applied to predict the drug response of corresponding CRC patients to CPT-11-based chemotherapy.

[31]

RC

NM

65

Wnt-3A, R-spondin-1, EGF, Gastrin I, A83–01, SB202190.

77%

RC PDOs retain molecular features of the original tumors.

[32]

RC

Biopsy

96

Noggin, R-spondin 1, EGF, Gastrin, A83–01, SB202190, PGE2

86%

A living biobank was generated from advanced RC patients treated with neoadjuvant chemoradiotherapy in a phase III clinical trial.

[33]

PC

Biopsy and surgery

8

Wnt-3A, Noggin, R-spondin1, EGF, Gastrin, FGF10

80%

The tumor development progress from early-grade tumor formation to locally invasive carcinomas and even metastatic carcinomas is reappeared in the PC PDO-X model.

[20]

PC

Biopsy and surgery

101

Wnt-3A, Noggin, R-spondin-1, EGF, Gastrin I, FGF10, PGE2

73%

The gene mutational spectrum and transcriptional subtypes of PC PDOs are largely the same as those of human PC tissues. Novel driver oncogenes and unique clusters are identified based on PC PDOs.

[34]

PC

Biopsy and surgery

52

Noggin, R-spondin, EGF, Gastrin, A83–01, PGE2, FGF10

63%

The PC PDOs copy the histology and typical genetic alterations of human PC tissues. Drug screening of 76 new drugs provides evidence for the drug’s effectiveness in the clinic.

[35]

PC

Surgery and biopsy

44

Wnt-3A, Noggin, R-spondin1, EGF, Gastrin, FGF10

NM

The PDO-based prediction model successfully predicts the response in treatment-naive patients for front-line regimens but fails to predict the response in pretreated patients.

[36]

PC

Biopsy

10

Wnt-3A, Noggin, R-spondin1, EGF, Gastrin, A83–01, Y-27632, FGF10

NM

The mutational spectrum in PC PDO supernatants recapitulates this in the human PC tissues, which facilitates drug screening of PC PDOs in a shortened time frame.

[37]

PDAC

Surgery

17

Y-27632, FGF2, hydrocortisone, all-trans retinoic acid, Ascorbic acid, Insulin

85%

PDAC PDOs recapitulate the differentiation status, histology, phenotypic heterogeneity patient-specific physiologic changes of parental tumors.

[38]

PDAC

Biopsy and surgery

39

Wnt-3A, Noggin, Rspondin-1, Gastrin, FGF10

80%

Three functional subtypes based on the dependencies on R-spondin and Wnt are confirmed. The heterogeneity of Wnt niche independency of PDAC forms in tumor progression.

[21]

PDAC

Biopsy

25

Wnt-3A, Noggin, R-spondin1, EGF, Gastrin I, A83–01, PGE2, FGF10

67%

PDCA PDOs were successfully established using EUS-FNB at the time of initial diagnosis.

[39]

PDAC

Biopsy

18

Wnt-3A, Noggin, R-spondin1, EGF, Gastrin I, A83–01, Y-27632, FGF-10

83%

The drug screening of PDAC PDOs can inform therapeutic selection and patient stratification for PDAC patients, and identify gene signatures associated with new therapeutic response combined with omics data.

[40]

PDAC

Surgery

6

Wnt-3A, R-spondin1, EGF, Gastrin I, A83–01, Y-27632, FGF-10

NM

Nine metabolites in early recurrent PDAC PDOs are increased when compared with late recurrent PDOs, indicating that an increased anaplerotic metabolism and energy metabolism fasten the PDAC recurrence.

[41]

GC

Biopsy and surgery

15

Wnt-3A, Noggin, R-spondin-1, EGF, Gastrin, FGF10

NM

The genomic profiling of paired human GC tissues and GC PDOs is largely the same, including the similar KRAS alterations.

[42]

GC

NM

37

Wnt-3A, Noggin, R-spondin1, EGF, A83–01, FGF10, Nutlin-3

NM

Generation and analysis of GC PDOs reveal molecular signatures underlying distinct histopathological subtypes and independence of Wnt signaling.

[43]

GC

NM

46

Wnt-3A, Noggin, R-spondin-1, EGF, FGF10, Gastrin, A83–01, Y-27632

> 50%

A biobank of GC PDOs with distinct subtypes is established and the PDOs maintain similarity to the parental tumors for long.

[44]

GC

Surgery

24

Wnt, Noggin, R-spondin-1, EGF, Gastrin, FGF10, A83–01, Y-27632

NM

The living bank of GC PDOs may predict therapy response for individual patients.

[45]

GC

Surgery

7

Wnt, Noggin, R-spondin-1, EGF, Gastrin, FGF10, Y-27632

NM

RNA sequencing reveals that the PDOs closely resemble the primary tumor tissue.

[46]

GC

MA

11

Wnt-3A, Noggin, R-spondin1, EGF, Gastrin, A83–01, Y-27632, FGF10

92%

GC MADOs copy the histology, and genomic feature of the original MA cancer cells.

[47]

PLC

Surgery

8

EGF, Gastrin I, A83–01, FGF10, HGF, FSK, Y-27632, dexamethasone

47%

PDOs of PLC (including HCC, CAC, and CHC) copy the histology and gene signature of the parental human PLC tissues.

[25]

PLC

Surgery and biopsy

27

Wnt-3A, Noggin, R-spondin, EGF, Gastrin, A83–01, FGF-10, HGF, FSK

NM

Drug screening of 129 drugs was performed using PLC PDO model.

[48]

HCC

Biopsy

10

Wnt-3A, Rspondin-1, Gastrin, EGF, A83–01 FGF10, HGF, FSK

26%

HCC PDOs maintain the morphology, HCC tumor markers and genetic heterogeneity of the original human HCC tissues.

[49]

EADC

Surgery

10

Wnt-3A, Noggin, R-Spondin-1, EGF, A83–01, SB202190, FGF10

31%

EADC PDOs maintain the morphology and molecular signature of the primary human EADC tissues. EADC PDOs and the original tumor tissues have the same clonal architecture.

[50]

ESCC

Biopsy

11

Wnt-3A, Noggin, R-Spondin, EGF, Gastrin, A83–01, SB202190

69%

ESCC PDOs recapitulate the histopathologic features of the original tumor tissues. Successful ESCC PDO generation is positively connected with poor response to radiation, chemotherapy and neoadjuvant chemotherapy.

[51]

BC

Surgery

6

R-spondin-1, EGF, Gastrin, A83–01, FSK, Y-27632

NM

The long-term cultured BC PDOs recapitulate the histopathology, gene signature of the original BC tissues.

[52]

  1. PDO Patient-derived organoid, GIC Gastrointestinal cancer, No. Number of samples, Ref Reference, CRC Colorectal cancer, PGE2 Prostaglandin E2, NM Not mentioned, mCRC Metastatic colorectal cancer, RC Rectal cancer, GC Gastric cancer, EGD Esophageal gastroduodenoscopy, RC Rectal cancer, PC Pancreatic cancer, PDO-X Patient-derived organoid- xenograft, PDAC Pancreatic adenocarcinoma, MA Malignant-ascites, MADOs Malignant-ascites derived organoids, HCC Hepatocellular carcinoma, FSK Forskolin, PLC Primary liver cancer, CAC Cholangiocarcinoma, CHC Combined HCC/CAC, EADC Esophageal adenocarcinoma, ESCC Esophageal squamous cell carcinoma, HGF Hepatocyte growth factor, CPT-11 Irinotecan, EUS-FNB Ultrasound-guided fine-needle biopsy, BC Biliary cancer