Netrin-1 blockade inhibits tumour growth and EMT features in endometrial cancer
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View abstract on PubMed
Summary
This summary is machine-generated.Netrin-1 blockade with antibody NP137 shows promise in endometrial cancer (EC). It reduced tumor progression in mice and patients, inhibited epithelial-to-mesenchymal transition (EMT), and improved chemotherapy response.
Area Of Science
- Oncology
- Cancer Biology
- Immunotherapy
Background
- Netrin-1 is upregulated in cancers, promoting tumor growth.
- Endometrial carcinoma (EC) shows high netrin-1 expression.
- Epithelial-to-mesenchymal transition (EMT) contributes to treatment resistance.
Purpose Of The Study
- To evaluate the efficacy of netrin-1 blockade using anti-netrin-1 antibody (NP137) in endometrial carcinoma.
- To investigate the mechanism of action of NP137, including its effect on EMT and the tumor microenvironment.
- To assess the combination therapy of NP137 with standard chemotherapy in an EC mouse model.
Main Methods
- Netrin-1 blockade using NP137 in an EC mouse model.
- Phase I clinical trial of NP137 in advanced EC patients.
- Tumor gene profiling, bulk RNA-seq, spatial transcriptomics, and single-cell RNA-seq on patient biopsies.
- Combination therapy of NP137 with carboplatin-paclitaxel in an EC mouse model.
Main Results
- NP137 demonstrated efficacy in reducing tumor progression in both mouse models and human EC patients (8/14 stable disease, 1 partial response).
- NP137 inhibited tumor epithelial-to-mesenchymal transition (EMT), induced cell death, and altered immune infiltrate.
- Combination therapy of NP137 with carboplatin-paclitaxel showed superior outcomes compared to chemotherapy alone in the EC mouse model.
Conclusions
- Netrin-1 blockade with NP137 is a promising clinical strategy for endometrial carcinoma.
- NP137 exhibits anti-tumor effects by inducing debulking and inhibiting EMT, potentially overcoming treatment resistance.
- This approach may enhance the efficacy of standard chemotherapies in advanced EC.
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