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Modulators of the Nrf2 Signaling Pathway Enhance the Cytotoxic Effect of Standard Chemotherapeutic Drugs on Organoids of Metastatic Colorectal Cancer

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The activity of known modulators of the Nrf2 signaling pathway (bardoxolone and brusatol) was studied on cultures of tumor organoids of metastatic colorectal cancer previously obtained from three patients. The effect of modulators was studied both as monotherapy and in combination with standard chemotherapy drugs used to treat colorectal cancer. The Nrf2 inhibitor brusatol and the Nrf2 activator bardoxolone have antitumor activity. Moreover, bardoxolone and brusatol also significantly enhance the effect of the chemotherapy drugs 5-fluorouracil, oxaliplatin, and irinotecan metabolite SN-38. Thus, bardoxolone and brusatol can be considered promising candidates for further preclinical and clinical studies in the treatment of colorectal cancer.

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Authors and Affiliations

  1. Higher School of Economics, Moscow, Russia

    A. V. Razumovskaya, M. O. Silkina, S. V. Nikulin & A. G. Tonevitsky

  2. National Medical Research Center of Radiology, Ministry of Health of the Russian Federation, Obninsk, Russia

    A. V. Razumovskaya, M. O. Silkina, S. V. Nikulin & B. Ya. Alekseev

  3. Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology, Ministry of Health of the Russian Federation, Moscow, Russia

    S. V. Nikulin

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  1. A. V. Razumovskaya
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  2. M. O. Silkina
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Correspondence to S. V. Nikulin.

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Translated from Kletochnye Tekhnologii v Biologii i Meditsine, No. 4, pp. 283-288, December, 2023

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Razumovskaya, A.V., Silkina, M.O., Nikulin, S.V. et al. Modulators of the Nrf2 Signaling Pathway Enhance the Cytotoxic Effect of Standard Chemotherapeutic Drugs on Organoids of Metastatic Colorectal Cancer. Bull Exp Biol Med 176, 703–708 (2024). https://doi.org/10.1007/s10517-024-06093-0

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