Drug Repurposing Approach Identifies a Synergistic Drug Combination of an Antifungal Agent and an Experimental Organometallic Drug for Melanoma Treatment.

Details

Serval ID
serval:BIB_A4EEAB69A9FB
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Drug Repurposing Approach Identifies a Synergistic Drug Combination of an Antifungal Agent and an Experimental Organometallic Drug for Melanoma Treatment.
Journal
Molecular pharmaceutics
Author(s)
Riedel T., Demaria O., Zava O., Joncic A., Gilliet M., Dyson P.J.
ISSN
1543-8392 (Electronic)
ISSN-L
1543-8384
Publication state
Published
Issued date
02/01/2018
Peer-reviewed
Oui
Volume
15
Number
1
Pages
116-126
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
By screening a drug library comprising FDA approved compounds, we discovered a potent interaction between the antifungal agent haloprogin and the experimental organometallic drug RAPTA-T, to synergistically induce cancer cell killing. The combination of these two small molecules, even at low doses, elicited an improved therapeutic response on tumor growth over either agent alone or the current treatment used in the clinic in the highly aggressive syngeneic B16F10 melanoma tumor model, where classical cytotoxic chemotherapeutic agents show little efficacy. The combination with the repurposed chemodrug haloprogin provides the basis for a new powerful treatment option for cutaneous melanoma. Importantly, because synergistic induction of tumor cell death is achieved with low individual drug doses, and cellular targets for RAPTA-T are different from those of classical chemotherapeutic drugs, a therapeutic strategy based on this approach could avoid toxicities and potentially resistance mechanisms, and could even inhibit metastatic progression.
Keywords
RAPTA-T, antifungal agent, drug discovery, haloprogin, high-throughput screening, melanoma, organometallic drug
Pubmed
Web of science
Open Access
Yes
Create date
16/11/2018 11:25
Last modification date
20/08/2019 15:10
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