Histone deacetylase-based dual targeted inhibition in multiple myeloma.

Autor: Ferro A; School of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland.; Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, Geneva, Switzerland., Pantazaka E; Synthetic Organic Chemistry Laboratory, Department of Chemistry, University of Patras, Patras, Greece.; Laboratory of Biochemistry/Metastatic Signaling, Section of Genetics, Cell Biology, and Development, Department of Biology, University of Patras, Patras, Greece., Athanassopoulos CM; Synthetic Organic Chemistry Laboratory, Department of Chemistry, University of Patras, Patras, Greece., Cuendet M; School of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland.; Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, Geneva, Switzerland.
Jazyk: angličtina
Zdroj: Medicinal research reviews [Med Res Rev] 2023 Nov; Vol. 43 (6), pp. 2177-2236. Date of Electronic Publication: 2023 May 16.
DOI: 10.1002/med.21972
Abstrakt: Despite enormous advances in terms of therapeutic strategies, multiple myeloma (MM) still remains an incurable disease with MM patients often becoming resistant to standard treatments. To date, multiple combined and targeted therapies have proven to be more beneficial compared to monotherapy approaches, leading to a decrease in drug resistance and an improvement in median overall survival in patients. Moreover, recent breakthroughs highlighted the relevant role of histone deacetylases (HDACs) in cancer treatment, including MM. Thus, the simultaneous use of HDAC inhibitors with other conventional regimens, such as proteasome inhibitors, is of interest in the field. In this review, we provide a general overview of HDAC-based combination treatments in MM, through a critical presentation of publications from the past few decades related to in vitro and in vivo studies, as well as clinical trials. Furthermore, we discuss the recent introduction of dual-inhibitor entities that could have the same beneficial effects as drug combinations with the advantage of having two or more pharmacophores in one molecular structure. These findings could represent a starting-point for both reducing therapeutic doses and lowering the risk of developing drug resistance.
(© 2023 The Authors. Medicinal Research Reviews published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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