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Table 2 Precision treatment for chemoradiotherapy using GIC PDOs

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

Cancer type

Chemotherapy drugs

Assay

Key findings

Ref.

CRC

OXA, 5-FU, DDP, CPT-11, DOC, GEM

CTG

Organoid technology allows personalized treatment design for chemotherapy.

[22]

CRC

5-FU, OXA

CTG

Drug response between PDOs and PDXs were fairly concordant for OXA but were inconsistent for 5-FU.

[26]

CRC

5-FU, OXA, CPT-11, Capecitabine, Folinic acid

CTG

The sensitivity, specificity, and accuracy rates of the CRC PDOs for predicting chemotherapy responses are 63.33, 94.12, and 79.69%, respectively.

[64]

CRC

OXA

Single-Cell RNA-Seq

The technologies of Single-cell RNA-Seq and drug-screening based on CRC PDOs help to find cancer heterogeneity.

[65]

CRC

Raltitrexed, OXA, MMC, GEM, 5-FU, Lobaplatin, Abraxane

CCK-8

Raltitrexed has the most significant hyperthermia synergism among the common hyperthermic intraperitoneal chemotherapy drugs in CRC PDOs.

[66]

mCRC

5-FU, OXA, CPT-11

CTG

The drug tests based on mCRC PDOs successfully predict the drug response to CPT-11 but fail to predict drug response to 5-FU plus OXA.

[31]

mCRC

5-FU, OXA, CPT-11, SN-38

CTG

mCRC PDOs show sensitivities to 5-FU, SN-38, the same as drug responses in clinic.

[67]

mCRC

Radiation, 5-FU, OXA

Optical metabolic imaging

The drug screening of mCRC PDOs shows promise to predict chemotherapy/radiation sensitivity for patients. It prospectively predicts response for a mCRC patient treated with re-treatment of FOLFOX chemotherapy.

[68]

mCRC

MMC, OXA

Live-cell imaging

Peritoneal metastasis-derived organoids can be applied to evaluate HIPEC regimens for mCRC patients.

[69]

mCRC

5-FU, OXA, CPT-11

CTG

The mCRC PDO-Sponge model keeping the similar expression level of lamin-A as their primary tumor tissues successfully predict FO chemotherapeutic regimen sensitivity.

[70]

RC

5FU, LV, OXA, Radiation

CTG

RC PDOs responses to chemoradiotherapy associated with responses in clinic. RC PDOs display the heterogeneous sensitivity to chemotherapy the same as in clinical.

[32]

RC

5-FU, CPT-11, Radiation

CTG

The sensitivity, specificity, and accuracy rates of the RC PDOs for predicting chemotherapy responses are 78.01, 91.97, and 84.43%, respectively.

[33]

PC

GEM, PTX, 5-FU, OXA, SN-38

CTG

PDOs exhibit heterogeneous responses to chemotherapy. PDO chemosensitivity profiles can mimic patient outcomes. SMAD4-deleted PC PDOs is sensitive to GEM.

[34]

PC

GEM, 5-FU, DDP, CBP, PTX, SN-38, OXA, DOC, NVB, VLB, CPT-11, CPT

CTG

Chemotherapy responses of PC PDOs indicate positive correlation with drug responses of patients in clinic.

[35]

PDAC

GEM, 5-FU, PTX, OXA, CPT-11

CTG

Pharmacotyping based on drug screening of PDCA PDOs has the potential for guiding postoperative adjuvant chemotherapeutic selection for PDCA patients undergoing surgery within the perioperative recovery period.

[71]

PDAC

FOLFIRINOX, GEM, Abraxane

MTS

PDAC PDOs display patient-specific chemotherapeutic sensitivities, and the response of PDO in vitro to FOLFIRINOX and GEM/Abraxane treatment was consistent with that of PDX in vivo.

[72]

PDAC

5-FU, DOC, doxorubicin, VP, GEM, CPT-11, MMC, OXA, PTX

Ki-67 staining

The accuracy rates of the PDOs from treatment-naive patients for predicting first-line regimens and second-line regimens are 91.1 and 80.0%, respectively. The accuracy rate of the PDOs from pretreated patients falls into 40.0%.

[36]

PDAC

Radiation

CTG

The combination of magnetic field and radiation show superior efficacy than monotherapy in PDAC PDOs.

[73]

mPC

GEM, Abraxane

CTG

The response of PDX-derived organoids and PDX models to GEM correlates with drug response in matched patients.

[57]

mPC

OXA

Organoid size

There is an excellent synergy of OXA and neoadjuvant photodynamic therapy without augment of toxicity based on mPC PDOs.

[74]

GC

DDP, OXA, 5-FU, CPT-11

CTG

Concordant cytotoxicity with chemotherapy drugs is found in GC PDOs from biopsy and surgical samples.

[42]

GC

5-FU, DDP, OXA, EPI, PTX

CTG

Common 5-FU and DDP resistances, and good OXA, EPI and PTX responses, are observed using GC PDO model.

[44]

GC

5-FU, OXA, CPT-11, EPI, DOC.

Annexin V/PI staining

An active conventional chemotherapeutic drug and a potential resistance pattern can be defined for each cancer organoid line.

[45]

GC

OXA, 5-FU, DDP, DOC, CPT-11, EPI, PTX

CCK-8

MADOs exhibit heterogeneous responses to standard-of-care chemotherapeutics.

[47]

GC

EPI, OXA,5-FU.

Live/Dead staining

PDOs of GC is useful to predict therapy response for individual patient in clinic.

[46]

GC

Nab-paclitaxel, 5-FU, EPI

CCK8

The GC PDOs is more sensitive to nab-paclitaxel than 5-FU and EPI.

[75]

PLC

Panobinostat, Ixazomib, Bortezomib, Daunorubicin, Topotecan, Plicamycin.

CTG

There used to be no approach to predict the response of human cancers to proteasome inhibitors, HDAC inhibitors, microtubule inhibitors. The drug testing based on PDO model has the potential to address the obstacles.

[48]

EC

5-FU

Organoid size

Cancer cells with high CD44 expression and autophagy are enriched in 5-FU resistance PDOs.

[51]

EADC

5-FU, EPI, DDP

CTG

The chemotherapy resistance for most EADC PDOs resembles the poor response to neo-adjuvant chemotherapy in EDAC patients.

[50]

GBC

VP

CTG

GEM-resistant and high YAP1-expressed GBC PDOs are sensitive to VP treatment.

[76]

mGIC

PTX, 5-FU, DDP

CTG

mGIC PDOs have a high accuracy value in forecasting response to chemotherapy in an individual patient.

[53]

  1. PDOs Patient-derived organoids, Ref Reference, CRC Colorectal cancer, CTG CellTiter-Glo, mCRC Metastatic colorectal cancer, RC Rectal cancer, GC Gastric cancer, PC Pancreatic cancer, PDAC Pancreatic adenocarcinoma, PLC Primary liver cancer, EC Esophageal cancer, EADC Esophageal adenocarcinoma, mGIC Metastatic gastrointestinal cancer, OXA Oxaliplatin, 5-FU 5-Fluorouracil, DDP Cisplatin, CPT-11 Irinotecan, PTX Paclitaxel, DOC Docetaxel, LV Leucovorin, GEM Gemcitibine, MMC Mitomycin C, CBP Carboplatin, EPI Epirubicin, NVB Vinorelbine, VLB Vinblastine, CPT Camptothecin, PI Propidium iodide, CAFs Cancer-associated fibroblasts, PDT Photodynamic therapy, CCK-8 Cell counting kit-8, HIPEC Hyperthermic intraperitoneal chemotherapy, DPYD/DPD Dihydrothymine dehydrogenase, FOLFIRINOX Oxaliplatin, leucovorin, irinotecan, 5-fluorouracil, MTA-3 (4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt, VP Etoposide, MADOs Malignant-ascites derived organoids