Background: Dual-targeting in cancer treatment by a single drug is an unconventional approach in relation to drug combinations. The rationale for the development of dual-targeting agents is to overcome incomplete efficacy and drug resistance frequently present when applying individual targeting agents. Consequently,-a more favorable outcome of cancer treatment is expected with dual-targeting strategies. Methods: We reviewed the literature, concentrating on the association between clinically relevant and/or novel dual inhibitors with the potential to modulate multidrug resistant phenotype of cancer cells, particularly the activity of P-glycoprotein. A balanced analysis of content was performed to emphasize the most important findings and optimize the structure of this review. Results: Two-hundred and forty-five papers were included in the review. The introductory part was interpreted by 9 papers. Tyrosine kinase inhibitors’ role in the inhibition of P-glycoprotein and chemosensitization was illustrated by 87 papers. The contribution of natural-based compounds in overcoming multidrug resistance was reviewed using 92 papers, while specific dual inhibitors acting against microtubule assembling and/or topoisomerases were described with 55 papers. Eleven papers gave an insight into a novel and less explored approach with hybrid drugs. Their influence on P-glycoprotein and multidrug resistance was also evaluated. Conclusion: These findings bring into focus rational anticancer strategies with dual-targeting agents. Most evaluated synthetic and natural drugs showed a great potential in chemosensitization. Further steps in this direction are needed for the optimization of anticancer treatment.
Dual inhibitors as a new challenge for cancer multidrug resistance treatment / T. Stankovic, J. Dinic, A. Podolski-Renic, L. Musso, S.S. Buric, S. Dallavalle, M. Pesic. - In: CURRENT MEDICINAL CHEMISTRY. - ISSN 0929-8673. - 26:33(2019), pp. 6074-6106. [10.2174/0929867325666180607094856]
Dual inhibitors as a new challenge for cancer multidrug resistance treatment
L. Musso;S. Dallavalle
;
2019
Abstract
Background: Dual-targeting in cancer treatment by a single drug is an unconventional approach in relation to drug combinations. The rationale for the development of dual-targeting agents is to overcome incomplete efficacy and drug resistance frequently present when applying individual targeting agents. Consequently,-a more favorable outcome of cancer treatment is expected with dual-targeting strategies. Methods: We reviewed the literature, concentrating on the association between clinically relevant and/or novel dual inhibitors with the potential to modulate multidrug resistant phenotype of cancer cells, particularly the activity of P-glycoprotein. A balanced analysis of content was performed to emphasize the most important findings and optimize the structure of this review. Results: Two-hundred and forty-five papers were included in the review. The introductory part was interpreted by 9 papers. Tyrosine kinase inhibitors’ role in the inhibition of P-glycoprotein and chemosensitization was illustrated by 87 papers. The contribution of natural-based compounds in overcoming multidrug resistance was reviewed using 92 papers, while specific dual inhibitors acting against microtubule assembling and/or topoisomerases were described with 55 papers. Eleven papers gave an insight into a novel and less explored approach with hybrid drugs. Their influence on P-glycoprotein and multidrug resistance was also evaluated. Conclusion: These findings bring into focus rational anticancer strategies with dual-targeting agents. Most evaluated synthetic and natural drugs showed a great potential in chemosensitization. Further steps in this direction are needed for the optimization of anticancer treatment.File | Dimensione | Formato | |
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