Histone deacetylase and DNA topoisomerase II dual target (HDAC/Topo II)

The combined targeting of Histone Deacetylase (HDAC) and DNA Topoisomerase II is a therapeutic strategy designed to exploit the synergistic relationship between epigenetic modulation and DNA damage induction. HDACs are enzymes that remove acetyl groups from histones, maintaining a condensed chromatin state that restricts access to DNA (PMID: 15150113). DNA Topoisomerase II is essential for resolving DNA topological constraints during replication and transcription by creating transient double-strand breaks (PMID: 12460924). Inhibition of HDACs leads to histone hyperacetylation and chromatin relaxation, which significantly increases the accessibility of DNA to Topoisomerase II inhibitors. This interaction results in an enhanced accumulation of lethal DNA double-strand breaks and the potentiation of apoptotic signaling in malignant cells. This dual-pathway approach is primarily investigated in oncology to overcome resistance to conventional Topoisomerase II poisons and to improve therapeutic outcomes in both hematologic and solid malignancies (PMID: 23614515).

Other names

HDAC and Topoisomerase II dual inhibitionHDAC-Topo II pathway interactionHistone deacetylase and DNA topoisomerase II synergyEpigenetic and DNA damage pathway interaction

Dual inhibition of HDAC and Topoisomerase II. HDAC inhibition promotes an open chromatin configuration through histone hyperacetylation, which increases the accessibility of DNA to Topoisomerase II inhibitors. This leads to the stabilization of Topoisomerase II-DNA cleavage complexes, resulting in increased double-strand breaks and apoptosis (PMID: 15150113, PMID: 16432171).