1. Perhexiline: Old Drug, New Tricks? A Summary of Its Anti-Cancer Effects.
- Author
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Dhakal, Bimala, Tomita, Yoko, Drew, Paul, Price, Timothy, Maddern, Guy, Smith, Eric, and Fenix, Kevin
- Subjects
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ANTINEOPLASTIC agents , *CANCER cell growth , *CARNITINE palmitoyltransferase , *DRUG development , *FATTY acids - Abstract
Cancer metabolic plasticity, including changes in fatty acid metabolism utilisation, is now widely appreciated as a key driver for cancer cell growth, survival and malignancy. Hence, cancer metabolic pathways have been the focus of much recent drug development. Perhexiline is a prophylactic antianginal drug known to act by inhibiting carnitine palmitoyltransferase 1 (CPT1) and 2 (CPT2), mitochondrial enzymes critical for fatty acid metabolism. In this review, we discuss the growing evidence that perhexiline has potent anti-cancer properties when tested as a monotherapy or in combination with traditional chemotherapeutics. We review the CPT1/2 dependent and independent mechanisms of its anti-cancer activities. Finally, we speculate on the clinical feasibility and utility of repurposing perhexiline as an anti-cancer agent, its limitations including known side effects and its potential added benefit of limiting cardiotoxicity induced by other chemotherapeutics. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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