Valproic Acid and Breast Cancer: State of the Art in 2021

SIMPLE SUMMARY: Breast cancer (BC) is the most common cancer diagnosed among women worldwide. Despite numerous studies, the pathogenesis of BC is still poorly understood, and effective therapy of this disease remains a challenge for medicine. This article provides the current state of knowledge of the impact of valproic acid (VPA) on different histological subtypes of BC, used in monotherapy or in combination with other active agents in experimental studies in vitro and in vivo. The comprehensive review highlights the progress that has been made on this topic recently. ABSTRACT: Valproic acid (2-propylpentanoic acid, VPA) is a short-chain fatty acid, a member of the group of histone deacetylase inhibitors (HDIs). VPA has been successfully used in the treatment of epilepsy, bipolar disorders, and schizophrenia for over 50 years. Numerous in vitro and in vivo pre-clinical studies suggest that this well-known anticonvulsant drug significantly inhibits cancer cell proliferation by modulating multiple signaling pathways. Breast cancer (BC) is the most common malignancy affecting women worldwide. Despite significant progress in the treatment of BC, serious adverse effects, high toxicity to normal cells, and the occurrence of multi-drug resistance (MDR) still limit the effective therapy of BC patients. Thus, new agents which improve the effectiveness of currently used methods, decrease the emergence of MDR, and increase disease-free survival are highly needed. This review focuses on in vitro and in vivo experimental data on VPA, applied individually or in combination with other anti-cancer agents, in the treatment of different histological subtypes of BC.