Repurposing carbamazepine in oncology and rare genetic diseases: A clinical update

Abstract Carbamazepine is an antiepileptic drug also used for neuropathic pain and mood stabilization. It is a strong enzyme inducer and autoinducer with multiple well-documented drug–drug interactions and adverse drug reactions. Widely licensed and in use since the 1960s, carbamazepine has well-characterized pharmacological, pharmacogenetic, and safety profiles, and remains extensively used in neurology and psychiatry. In 2024, carbamazepine was recommended for inclusion in the World Health Organization list of essential medicines. Carbamazepine has a complex mode of action that includes neuronal stabilization, neuroprotection, neurotransmitter modulation, enhancement of autophagy, and anti-inflammatory effects. These make carbamazepine a good candidate for drug repurposing in oncology, genetic diseases, neurodegeneration, and systemic inflammation. Recent advances in precision medicine, genomics, and on/off-target drug repositioning have enabled the identification of new carbamazepine molecular targets for novel applications in different therapeutic modalities. This review highlights carbamazepine repurposing studies in cancers such as breast and colorectal, based on its mode of action. In addition, repurposing studies in genetic diseases such as metaphyseal achondroplasia and Fragile-X, as well as in neurodegenerative conditions such as amyotrophic lateral sclerosis and Alzheimer's dementia, are discussed. The pharmacological mechanisms and drug repurposing pathways are critically summarized in order to provide insights into their therapeutic potential and proposed future directions.