Modulating the microbiome as an approach to anticancer drug development

Arakelyan, J.; Choe, H.; Wu, C.; Rusanov, D.; Bardina, E.; Kirsanova, A.; Zakalyukina, Y.; Shmelev, N.; Tyurin, A.; Komarov, V.; Kushnarev, V.; Karnaukhov NS, D.G.; Vasilyev, E.; Dotse, E.; Chow, K.; Cho, W.; Tkachev, A.; Gushchin, A.; Babak, M.

Авторы: Arakelyan J., Choe HJ, Wu C., Rusanov DA, Bardina EE, Kirsanova AA, Zakalyukina YV, Shmelev NY, Tyurin AP, Komarov VY, Kushnarev V., Karnaukhov NS D’Cruz G., Vasilyev ES, Dotse E., Chow KT, Cho WC, Tkachev AV, Gushchin AL, Babak MV
Журнал: Proceedings of the National Academy of Sciences of the United States of America
Том: 122
Номер: 44
Год издания: 2025
Издательство: National Academy of Sciences
Местоположение издательства: United States
Первая страница: 1
Последняя страница: 12
Номер статьи: e2417269122
DOI: 10.1073/pnas.2417269122
Аннотация: Recent studies have suggested that the commensal microbiome positively affects cancer prognosis and treatment outcomes. However, only a few strategies for regulating the microbiome composition have been reported. In this study, we identified gold(I) complexes that selectively inhibited nonbeneficial bacterial strains in vitro without affecting commensal Lactobacillus strains. In contrast, clinically used drugs demonstrated comparable effects on both commensal and noncommensal strains. Consistent with the in vitro results, the selected gold(I) complex induced favorable changes in the intratumoral and gastrointestinal microbiomes in vivo. Furthermore, its anticancer efficacy was found to be dependent on the composition of microbiome and correlated with the production of short-chain fatty acid bacterial metabolites. Structure-activity relationship studies have dissected the contribution of each structural component in both the in vivo efficacy and microbiome-modulating properties. Transcriptomic analysis of tumors revealed microbiome-associated gene signaling pathways. These findings provide valuable insights for future research on microbiome-modulating anticancer drugs, presenting potential avenues to optimize cancer treatment outcomes and mitigate side effects such as gastrointestinal dysbiosis. Furthermore, our study provides insights into the involvement of microbiome in the mechanism of action of metal-based chemotherapeutics.

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Modulating the microbiome as an approach to anticancer drug developmentстатья Исследовательская статья

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