The iron chelator deferasirox synergizes with chemotherapy to treat triple negative breast cancers.
Tury S1, Assayag F2, Bonin F1, Chateau-Joubert S3, Servely JL3,4, Vacher S1, Becette V5, Caly M6, Rapinat A7, Gentien D7, de la Grange P8, Schnitzler A1, Lallemand F1, Marangoni E2, Bièche I1,9, Callens C1.
J Pathol. 2018 Jun 7. doi: 10.1002/path.5104.

Abstract
To ensure their high proliferation rate, tumor cells display an iron metabolic disorder with increased iron needs, making them more susceptible to iron deprivation. This vulnerability could be a therapeutic target. In breast cancers, the development of
new therapeutic approaches is urgently needed for patients with triple negative tumors which frequently relapse after chemotherapy and suffer from a lack of targeted therapies. In this work, we demonstrated that deferasirox (DFX) synergizes with standard
chemotherapeutic agents such as with doxorubicin, cisplatin and carboplatin to inhibit cell proliferation and induce apoptosis and autophagy in triple-negative breast cancer (TNBC) cell lines. Moreover, the combination of DFX with doxorubicin and
cyclophosphamide delayed recurrences in breast cancer patient-derived xenografts without increasing the side-effects of chemotherapies alone or altering global iron storage of mice. Antitumor synergy of DFX and doxorubicin seems to involve down-
regulation of the PI3K and NF-κB pathways. Iron deprivation in combination with chemotherapy could thus help to improve the effectiveness of chemotherapy in TNBC patients without increasing toxicities. This article is protected by copyright. All rights
reserved.

KEYWORDS:
Breast cancer; chemotherapy; deferasirox; iron chelators; iron metabolism

PMID: 29876931 DOI: 10.1002/path.5104

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