Reversible p53 inhibition prevents cisplatin ototoxicity without blocking chemotherapeutic efficacy

  • Benkafadar N
  • Menardo J
  • Bourien J
  • et al.
N/ACitations
Citations of this article
21Readers
Mendeley users who have this article in their library.

Abstract

© 2016 The Authors. Published under the terms of the CC BY 4.0 license Cisplatin is a widely used chemotherapy drug, despite its significant ototoxic side effects. To date, the mechanism of cisplatin-induced ototoxicity remains unclear, and hearing preservation during cisplatin-based chemotherapy in patients is lacking. We found activation of the ATM-Chk2-p53 pathway to be a major determinant of cisplatin ototoxicity. However, prevention of cisplatin-induced ototoxicity is hampered by opposite effects of ATM activation upon sensory hair cells: promoting both outer hair cell death and inner hair cell survival. Encouragingly, however, genetic or pharmacological ablation of p53 substantially attenuated cochlear cell apoptosis, thus preserving hearing. Importantly, systemic administration of a p53 inhibitor in mice bearing patient-derived triple-negative breast cancer protected auditory function, without compromising the anti-tumor efficacy of cisplatin. Altogether, these findings highlight a novel and effective strategy for hearing protection in cisplatin-based chemotherapy.

Cite

CITATION STYLE

APA

Benkafadar, N., Menardo, J., Bourien, J., Nouvian, R., François, F., Decaudin, D., … Wang, J. (2016). Reversible p53 inhibition prevents cisplatin ototoxicity without blocking chemotherapeutic efficacy. EMBO Molecular Medicine, 9(1), 7–26. https://doi.org/10.15252/emmm.201606230

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free