# Histoculture drug response assay predicts chemotherapy efficacy and improves survival in gastrointestinal cancers

**Authors:** Shuang Wang, Na Fan, Han Li, Yang Li, Ping Hu, Dongliang Chen, Xiaohong Jiang, Lei Gao, Chenggang Yang, Dawei Yang

PMC · DOI: 10.3389/fonc.2025.1596253 · Frontiers in Oncology · 2025-07-16

## TL;DR

A drug response test called HDRA can predict chemotherapy effectiveness and improve survival in gastrointestinal cancer patients.

## Contribution

The study demonstrates that HDRA-guided treatment improves disease-free survival in gastrointestinal cancer patients.

## Key findings

- HDRA preserved tumor structure and microenvironment without altering key marker expressions.
- Combination chemotherapy regimens showed higher efficacy than single-agent therapies.
- HDRA-guided treatment was associated with longer disease-free survival in esophageal and gastric cancer patients.

## Abstract

The high incidence, substantial mortality, and marked heterogeneity in chemotherapy responses among gastrointestinal tumors accentuate the imperative for individualized treatment strategies. This study aims to evaluate the reliability and clinical significance of the histoculture drug response assay (HDRA) in predicting chemotherapy sensitivity and prognosis. Specifically, it focuses on Chinese patients diagnosed with gastrointestinal cancers.

This study enrolled 283 patients with gastrointestinal tumors, comprising 124 esophageal cancer cases, 92 gastric/cardia cancer cases, and 67 colorectal cancer cases. Immunohistochemistry was conducted to assess tumor structure integrity and the expression of Ki - 67, CD31, and E - cadherin before and after the HDRA assay. HDRA evaluated the efficacy and inhibition rates of single and combination chemotherapy regimens. Moreover, the effect of HDRA - guided treatment on patient survival was analyzed.

The results indicated that HDRA effectively preserved the three-dimensional structure and microenvironment of gastrointestinal tumors, as no significant changes were observed in the expression of Ki-67, CD31, or E-cadherin. Furthermore, combination regimens showed significantly higher efficacy and inhibition rates than single - agent therapies. Notably, platinum-based combination therapy was most effective in esophageal cancer. Survival analysis revealed that esophageal and gastric cancer patients receiving HDRA - sensitive regimens (HDRA group) had significantly longer disease - free survival (DFS) compared to those on non - sensitive regimens (N - HDRA group) and untreated patients. Cox regression analysis indicated that HDRA-guided treatment serves as a protective factor for DFS (hazard ratio, HR<1).

In summary, the HDRA assay represents a reliable assay for accurately evaluating chemotherapy regimens, thereby furnishing guidance for individualized treatment in gastrointestinal cancer patients.

## Linked entities

- **Genes:** Mki67 (antigen identified by monoclonal antibody Ki 67) [NCBI Gene 17345], PECAM1 (platelet and endothelial cell adhesion molecule 1) [NCBI Gene 5175], shg (shotgun) [NCBI Gene 37386]
- **Diseases:** esophageal cancer (MONDO:0007576), gastric/cardia cancer (MONDO:0003834), colorectal cancer (MONDO:0005575)

## Full-text entities

- **Genes:** TENM1 (teneurin transmembrane protein 1) [NCBI Gene 10178] {aka ODZ1, ODZ3, TEN-M1, TEN1, TNM, TNM1}, CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, CREBBP (CREB binding lysine acetyltransferase) [NCBI Gene 1387] {aka CBP, KAT3A, MKHK1, RSTS, RSTS1}, CDH1 (cadherin 1) [NCBI Gene 999] {aka Arc-1, BCDS1, CD324, CDHE, ECAD, LCAM}, LBP (lipopolysaccharide binding protein) [NCBI Gene 3929] {aka BPIFD2}, PECAM1 (platelet and endothelial cell adhesion molecule 1) [NCBI Gene 5175] {aka CD31, CD31/EndoCAM, GPIIA', PECA1, PECAM-1, endoCAM}, ERBB2 (erb-b2 receptor tyrosine kinase 2) [NCBI Gene 2064] {aka CD340, HER-2, HER-2/neu, HER2, MLN 19, MLN-19}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}
- **Diseases:** N (MESH:C536108), Tumor (MESH:D009369), Gastrointestinal tumors (MESH:D005770), necrosis (MESH:D009336), metastasis (MESH:D009362), disease (MESH:D004194), Esophagus cancer (MESH:D004938), colorectal cancer (MESH:D015179), toxicity (MESH:D064420), cardia/gastric cancer (MESH:D013274), HL (MESH:C538324)
- **Chemicals:** DMSO (MESH:D004121), N (MESH:D009584), 5-FU (MESH:D005472), CO2 (MESH:D002245), paclitaxel (MESH:D017239), cisplatin (MESH:D002945), CY (MESH:D003545), MTT (MESH:C070243), CDDP (-), TS-1 (MESH:C103828), platinum (MESH:D010984), DAB (MESH:C000469), formalin (MESH:D005557), hydrogen peroxide (MESH:D006861), sodium citrate (MESH:D000077559), xylene (MESH:D014992), ethanol (MESH:D000431), LEU (MESH:D007930), CPT-11 (MESH:D000077146)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12307191/full.md

## References

37 references — full list in the complete paper: https://tomesphere.com/paper/PMC12307191/full.md

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Source: https://tomesphere.com/paper/PMC12307191