Evaluating the efficacy and microenvironment changes of HER2 + gastric cancer during HLX02 and Endostar treatment
Jianye Liang1, Wei Dai1, Zhipeng Li1
1Department of Medical Imaging, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China.
Background And Objectives:
Trastuzumab is an important targeted drug for HER2-positive gastric cancer. The treatment efficacy of a more cost-effective and accessible trastuzumab biosimilar, HLX02, was not well investigated, especially when combined with antiangiogenic treatment. In addition, the tumour microenvironment detected by functional MRI was still unclear during treatment. This study attempts to evaluate the therapeutic effect of antiangiogenic agents combined with HLX02 in a HER2-positive gastric cancer xenograft model and to detect microenvironmental changes using intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI).
Materials And Methods:
We subcutaneously injected MKN-45 human gastric cancer cells into BALB/C nude mice to establish a tumour model. Twenty-eight mice were divided into four groups and treated with saline (Group 1), Endostar (Group 2), trastuzumab biosimilar HLX02 (Group 3), or the combination of Endostar and HLX02 (Group 4). We then performed IVIM-DWI before and at different time points after treatment. HE, HER2, TUNEL, E-cadherin staining, and α-SMA and CD31 double-staining were used to confirm the pathological changes.
Results:
Group 4 demonstrated the smallest tumour volume at the end of treatment. The D value in Group 4 increased more dramatically, with the highest value on Day 20, compared with the other groups. Perfusion-related parameters (D* and f values) in Groups 2 and 4 increased initially and reversed after Day 10. Group 4 showed the lowest CD31 and HER2 and the highest TUNEL- and E-cadherin-positive staining rates. The D value was positively correlated with TUNEL but negatively correlated with HER2 staining. The D* and f values had positive correlations with CD31 and E-cadherin expression and the vessel maturity index.
Conclusions:
The trastuzumab biosimilar drug HLX02 exhibited good treatment efficacy in HER2-positive gastric cancer, especially when combined with Endostar. IVIM-DWI can noninvasively monitor the process of vascular normalization and reflect the treatment effect early at the molecular level.
Insights
The trastuzumab biosimilar HLX02 combined with Endostar effectively treats HER2-positive gastric cancer. Intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) noninvasively monitors treatment response and tumor microenvironment changes.
Area of Science:
- Oncology
- Pharmacology
- Medical Imaging
Background:
- Trastuzumab is a key targeted therapy for HER2-positive gastric cancer.
- The efficacy of the biosimilar HLX02, particularly with antiangiogenic agents, requires further investigation.
- Tumor microenvironment changes during treatment are not well understood.
Purpose of the Study:
- To evaluate the therapeutic effect of HLX02 combined with antiangiogenic agents in a HER2-positive gastric cancer xenograft model.
- To assess microenvironmental changes using intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI).
Main Methods:
- Established a human gastric cancer xenograft model (MKN-45 cells in nude mice).
- Treated mice with saline, Endostar, HLX02, or Endostar + HLX02.
- Utilized IVIM-DWI for imaging and performed histological analyses (HE, HER2, TUNEL, E-cadherin, α-SMA, CD31).
Main Results:
- The combination of Endostar and HLX02 resulted in the smallest tumor volume.
- IVIM-DWI showed increased D values in the combination group, correlating with increased apoptosis (TUNEL) and decreased HER2 expression.
- Perfusion parameters (D*, f) indicated vascular normalization, correlating with vessel maturity.
Conclusions:
- The trastuzumab biosimilar HLX02 demonstrates significant efficacy in HER2-positive gastric cancer, enhanced by combination with Endostar.
- IVIM-DWI serves as a valuable noninvasive tool for monitoring vascular normalization and early treatment effects at a molecular level.
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