Targeting Cancer Cell Energy Metabolism in Colorectal Cancer: Opportunities and Challenges from Drug Repositioning
Lorenzo Tomassini1, Teresa Pacifico1, Giovanni Monteleone1,2
1Department of Systems Medicine, University of Rome "Tor Vergata", 00133 Rome, Italy.
Cells
|December 24, 2025
Summary
Drug repositioning offers a cost-effective strategy to find new colorectal cancer (CRC) therapies by targeting cancer cell metabolism. Repurposed non-oncologic drugs can disrupt CRC growth and enhance current treatments.
Area of Science:
- Oncology
- Pharmacology
- Metabolic Research
Background:
- Colorectal cancer (CRC) is a leading cause of cancer mortality worldwide.
- Targeting cancer cell metabolism disrupts tumor growth and resistance.
- Drug repositioning accelerates the development of novel cancer therapies.
Purpose of the Study:
- To evaluate non-oncologic drugs for repositioning against colorectal cancer.
- To explore how these drugs exploit metabolic vulnerabilities in CRC cells.
- To assess the potential of drug repositioning for personalized CRC treatment.
Main Methods:
- Review of mechanistic, preclinical, and clinical findings on drug repositioning in CRC.
- Analysis of how antidiabetic, cardiovascular, anti-inflammatory, antidepressant, and anthelmintic agents affect CRC metabolism.
- Examination of effects on glycolysis, oxidative phosphorylation, and mitochondrial bioenergetics.
Main Results:
- Repurposed drugs target key metabolic pathways and regulators (e.g., AMPK/mTOR) in CRC.
- These agents interfere with essential bioenergetic and biosynthetic processes in cancer cells.
- Drug repositioning can enhance the efficacy of standard CRC chemotherapies and immunotherapies.
Conclusions:
- Targeting CRC metabolism via drug repositioning is a promising therapeutic strategy.
- Repurposed drugs offer a viable approach to overcome treatment resistance and improve outcomes.
- Addressing translational challenges is crucial for clinical implementation of these therapies.
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