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An Innovative Drug Repurposing Approach to Restrain Endometrial Cancer Metastatization
Federica Torricelli1, Elisabetta Sauta1,2, Veronica Manicardi1,2,3
1Laboratory of Translational Research, Azienda USL-IRCCS di Reggio Emilia, Viale Risorgimento 80, 42123 Reggio Emilia, Italy.
Background:
Endometrial cancer (EC) is the most common gynecologic tumor and the world's fourth most common cancer in women. Most patients respond to first-line treatments and have a low risk of recurrence, but refractory patients, and those with metastatic cancer at diagnosis, remain with no treatment options. Drug repurposing aims to discover new clinical indications for existing drugs with known safety profiles. It provides ready-to-use new therapeutic options for highly aggressive tumors for which standard protocols are ineffective, such as high-risk EC.
Methods:
Here, we aimed at defining new therapeutic opportunities for high-risk EC using an innovative and integrated computational drug repurposing approach.
Results:
We compared gene-expression profiles, from publicly available databases, of metastatic and non-metastatic EC patients being metastatization the most severe feature of EC aggressiveness. A comprehensive analysis of transcriptomic data through a two-arm approach was applied to obtain a robust prediction of drug candidates.
Conclusions:
Some of the identified therapeutic agents are already successfully used in clinical practice to treat other types of tumors. This highlights the potential to repurpose them for EC and, therefore, the reliability of the proposed approach.
Insights
Drug repurposing offers new hope for high-risk endometrial cancer (EC) by identifying existing drugs for treatment. This computational approach reveals potential therapies for aggressive EC cases unresponsive to standard treatments.
Area of Science:
- Oncology
- Genomics
- Pharmacology
Background:
- Endometrial cancer (EC) is a common gynecologic malignancy.
- High-risk and metastatic EC patients often lack effective treatment options.
- Drug repurposing provides safe, existing medications for aggressive cancers.
Purpose of the Study:
- To identify novel therapeutic strategies for high-risk endometrial cancer.
- To leverage computational drug repurposing for aggressive EC treatment.
Main Methods:
- Comparative analysis of gene-expression profiles from metastatic and non-metastatic EC patients.
- Utilized publicly available transcriptomic data.
- Employed an integrated computational approach for drug candidate prediction.
Main Results:
- Identified potential drug candidates for high-risk endometrial cancer.
- Transcriptomic data analysis revealed therapeutic targets.
- The computational approach yielded robust predictions.
Conclusions:
- Repurposing existing drugs offers a viable treatment avenue for high-risk EC.
- Identified agents are already in clinical use for other cancers, validating the approach.
- This strategy provides new therapeutic options for aggressive EC.
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