HDAC and PI3K dual inhibitors in the treatment of cancers: Current status, trends, and solutions.

HDAC (Histone Deacetylase) and PI3K (Phosphoinositide 3-kinases) are two pivotal targets in cancer research. Individually, inhibitors targeting HDAC or PI3K have shown potent anticancer effects, particularly against various hematological malignancies. However, targeting either HDAC or PI3K alone often fails to fully control disease progression and may lead to drug resistance. A promising strategy to address these challenges is the development of single molecules that inhibit both HDAC and PI3K. Research indicates that dual inhibitors can synergistically enhance cell toxicity, suggesting a potent therapeutic effect. Despite being in the nascent stages, several significant studies have already documented the design and pharmacological activities of these dual-target inhibitors. This review delves into the dual-target inhibitors of HDAC and PI3K, exploring their design principles and pharmacological properties. This article covers the literature up to October 2025, aiming to provide contemporary insights and guidance for the future design and optimization of such multifaceted inhibitors.