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Mesothelin as a target for cervical cancer therapy
Korinna Jöhrens1, Lea Lazzerini2, Jana Barinoff2
1Department of Pathology, Charité-Universitätsmedizin Berlin, Campus Mitte, Charitéplatz 1, 10117, Berlin, Germany.
Archives of Gynecology and Obstetrics
|October 17, 2018
Summary
Mesothelin is highly expressed in cervical cancers, making it a potential therapeutic target. A novel drug conjugate demonstrated significant tumor regression in preclinical models, suggesting its use in cervical cancer treatment.
Area of Science:
- Oncology
- Immunotherapy
- Biomarker Discovery
Background:
- Mesothelin is overexpressed in various cancers, including ovarian and pancreatic cancers.
- Novel Mesothelin-targeted immunotherapies are in early clinical trials.
- Cervical cancer has not been previously considered a target for Mesothelin-directed therapies.
Purpose of the Study:
- To investigate Mesothelin expression in cervical carcinomas.
- To evaluate the therapeutic potential of a novel anti-Mesothelin drug conjugate in cervical cancer models.
Main Methods:
- Mesothelin expression was analyzed in 79 cervical carcinomas.
- Correlation of Mesothelin expression with tumor growth parameters was assessed.
- Dose-efficiency studies of Anetumab Ravtansine were performed in a Mesothelin-positive cervical cancer xenograft model in SCID mice.
Main Results:
- High Mesothelin expression was observed in 77% of cervical adenocarcinomas and 57% of squamous cell carcinomas.
- No significant correlation was found between Mesothelin levels and tumor grade, metastatic behavior, or lymph/hemangiosis.
- Anetumab Ravtansine (ADC) demonstrated dose-dependent therapeutic efficacy, inducing complete tumor regression in 88% of animals at 10 mg/kg twice weekly.
Conclusions:
- Mesothelin is a promising therapeutic target for cervical cancer.
- Histological determination of Mesothelin expression could be valuable in routine cervical carcinoma diagnostics.
- Further investigation into Mesothelin-directed therapies for cervical cancer is warranted.
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