doxorubicin + valproic acid

Doxorubicin + valproic acid is an investigational combination therapy consisting of the anthracycline chemotherapeutic agent doxorubicin and the histone deacetylase (HDAC) inhibitor valproic acid. Doxorubicin acts primarily by intercalating into DNA, inhibiting topoisomerase II, generating reactive oxygen species (ROS), and inducing apoptosis in cancer cells. Valproic acid, widely used as an anticonvulsant and mood stabilizer, also functions as a HDAC inhibitor at therapeutic concentrations; it increases histone acetylation leading to altered gene expression, promotes cell differentiation and apoptosis, enhances GABAergic neurotransmission in neural tissue, and can sensitize tumor cells to cytotoxic agents. Preclinical studies have demonstrated that this combination exerts synergistic anti-cancer effects in various cancer models including hepatocellular carcinoma (HCC) and anaplastic thyroid carcinoma. The synergy is attributed to enhanced induction of apoptosis via increased ROS generation, autophagy activation, cell cycle arrest at G2/M phase by doxorubicin potentiated through histone acetylation from valproic acid action. Additionally, valproic acid has been shown to increase cellular uptake of doxorubicin via caveolae-mediated endocytosis pathways[1][3]. Early-phase clinical trials have explored this combination for refractory or recurrent malignancies such as mesothelioma[7] and canine cancers[2].

Other names

doxorubicin and valproic acidDOX + VPA