Istradefylline protects from cisplatin-induced nephrotoxicity and peripheral neuropathy while preserving cisplatin antitumor effects - Archive ouverte HAL Access content directly
Journal Articles The Journal of clinical investigation Year : 2022

Istradefylline protects from cisplatin-induced nephrotoxicity and peripheral neuropathy while preserving cisplatin antitumor effects

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Noura Massri
Joseph Folger
Patrice Maboudou
  • Function : Author
Rodrigo Cunha

Abstract

Cisplatin is a potent chemotherapeutic drug that is widely used in the treatment of various solid cancers. However, its clinical effectiveness is strongly limited by frequent severe adverse effects, in particular nephrotoxicity and chemotherapy-induced peripheral neuropathy. Thus, there is an urgent medical need to identify novel strategies that limit cisplatin-induced toxicity. In the present study, we show that the FDA-approved adenosine A2A receptor antagonist istradefylline (KW6002) protected from cisplatin-induced nephrotoxicity and neuropathic pain in mice with or without tumors. Moreover, we also demonstrate that the antitumoral properties of cisplatin were not altered by istradefylline in tumor-bearing mice and could even be potentiated. Altogether, our results support the use of istradefylline as a valuable preventive approach for the clinical management of patients undergoing cisplatin treatment.
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Origin : Publication funded by an institution

Dates and versions

inserm-03865945 , version 1 (22-11-2022)

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Edmone Dewaeles, Kévin Carvalho, Sandy Fellah, Jaewon Sim, Nihad Boukrout, et al.. Istradefylline protects from cisplatin-induced nephrotoxicity and peripheral neuropathy while preserving cisplatin antitumor effects. The Journal of clinical investigation, 2022, 132 (22), pp.e152924. ⟨10.1172/JCI152924⟩. ⟨inserm-03865945⟩
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