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Papers of the Week


Papers: 12 Nov 2022 - 18 Nov 2022


2022 Nov 15


J Clin Invest


132


22

Editor's Pick

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

Authors

Dewaeles E, Carvalho K, Fellah S, Sim J, Boukrout N, Caillierez R, Ramakrishnan H, Van der Hauwaert C, Shankara J V, Martin N, Massri N, Launay A, Folger JK, de Schutter C, Larrue R, Loison I, Goujon M, Jung M, Le Gras S, Gomez-Murcia V, et al.
J Clin Invest. 2022 Nov 15; 132(22).
PMID: 36377661.

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.