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Sie sind hier: Startseite AK Hansen Publikationen Synergistic induction of apoptosis in resistant head and neck carcinoma and leukemia by alkoxyamide-based histone deacetylase inhibitors

Leandro A Alves Avelar, Christian Schrenk, Melf Sönnichsen, Alexandra Hamacher, Finn K Hansen, Julian Schliehe-Diecks, Arndt Borkhardt, Sanil Bhatia, Matthias U Kassack, and Thomas Kurz (2021)

Synergistic induction of apoptosis in resistant head and neck carcinoma and leukemia by alkoxyamide-based histone deacetylase inhibitors

European Journal of Medicinal Chemistry, 211:113095.

Targeting epigenetic dysregulation has emerged as a valuable therapeutic strategy in cancer treatment. Especially epigenetic combination therapy of histone deacetylase inhibitors (HDACi) with established anti-cancer drugs has provided promising results in preclinical and clinical studies. The structural optimization of alkoxyamide-based class I/IIb inhibitors afforded improved analogs with potent efficacy in cisplatin-resistant head and neck carcinoma cells and bortezomib-resistant leukemia cells. The most promising HDACi showed a superior synergistic cytotoxic activity as compared to vorinostat and class I HDACi in combination with cisplatin, leading to a full reversal of the chemoresistant phenotype in head and neck cancer cell lines, as well in combination with the proteasome inhibitors (bortezomib and carfilzomib) in a panel of leukemic cell lines. Furthermore, the most valuable alkoxyamide-based HDACi exhibited strong ex vivo anticancer efficacy against primary patient samples obtained from different therapy-resistant leukemic entities.

Cancer resistance, Chemosensitizing effects, Class I, Class IIb inhibitors, HDAC isozyme Profile, Histone deacetylases, Leukemia, Solid cancer