New Use for Old Drugs: The Protective Effect of Risperidone on Colorectal Cancer

Area of Science:

• Oncology
• Pharmacology
• Epidemiology

Background:

• Repurposing existing medications for new therapeutic uses is a growing area of interest.
• Second-generation antipsychotics (SGAs) are a class of drugs primarily used to treat psychiatric disorders.
• Investigating the potential anti-cancer effects of SGAs, such as risperidone, is warranted.

Purpose of the Study:

• To investigate the association between second-generation antipsychotic (SGA) drug exposure and colorectal cancer risk.
• To evaluate the anti-cancer effects of risperidone using a triple-model approach (population-based, cell, and animal studies).

Main Methods:

• Population-based study using Taiwan's National Health Insurance Research Database (1997-2013) comparing 101,989 colorectal cancer patients with 101,989 controls.
• Conditional logistic regression analyses to assess the association between SGA exposure and colorectal cancer risk.
• In vitro cell studies (SW480 cells) and in vivo animal studies (nude mice xenografts) to evaluate risperidone's anti-cancer mechanisms.

Main Results:

• SGAs were less frequently used in colorectal cancer patients compared to controls.
• A significant inverse association was observed between SGA use and colorectal cancer risk (adjusted OR=0.32).
• Risperidone demonstrated notable tumor inhibition, inducing apoptosis, increasing intracellular reactive oxygen species (ROS), and suppressing tumor proliferation in preclinical models.

Conclusions:

• This comprehensive triple-model study suggests an association between risperidone usage and a reduced risk of colorectal cancer.
• Findings support the potential of risperidone as an anti-cancer agent, warranting further clinical investigation.
• The study highlights the value of exploring existing drugs for novel oncological indications.