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Genetic and pharmacologic inhibition of eIF4E reduces breast cancer cell migration, invasion and metastasis

Menée à l'aide de modèles murins, cette étude suggère l'intérêt de la ribavarine, un inhibiteur du facteur elF4E, pour le traitement d'un cancer métastatique du sein

Translation initiation factor eIF4E is an oncogene that is commonly overexpressed in primary breast cancers and metastases. In this report, we report that a pharmacologic inhibitor of eIF4E function, ribavirin, safely and potently suppresses breast tumor formation. Ribavirin administration blocked the growth of primary breast tumors in several murine models and reduced the development of lung metastases in an invasive model. Mechanistically, eIF4E silencing or blockade reduced the invasiveness and metastatic capability of breast cancer cells in a manner associated with decreased activity of MMP-3 and MMP-9. Further, eIF4E silencing or ribavirin treatment suppressed features of epithelial-to-mesenchymal transition (EMT), a process crucial for metastasis. Our findings offer a preclinical rationale to explore broadening the clinical evaluation of ribavirin, currently being tested in patients with eIF4E-overexpressing leukemia, as a strategy to treat solid tumors such as metastatic breast cancer.

Cancer Research 2015

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