Research ArticleCancer

Targeting the XPO1-dependent nuclear export of E2F7 reverses anthracycline resistance in head and neck squamous cell carcinomas

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Science Translational Medicine  27 Jun 2018:
Vol. 10, Issue 447, eaar7223
DOI: 10.1126/scitranslmed.aar7223

Restoring balance in the nucleus

Despite recent advances in cancer treatment, resistance to cancer therapy and resulting mortality remain common in head and neck squamous cell carcinoma. In their search for the causes of treatment resistance, Saenz-Ponce et al. identified a mechanism dependent on the balance of two proteins that regulate transcription and these proteins’ localization within cancer cells. Specifically, the authors discovered that a transcriptional inhibitor called E2F7 is frequently mislocalized to the cytoplasm in these tumors, whereas its transcription-activating counterpart, E2F1, remains in the nucleus and drives transcription of treatment resistance genes. The authors also identified an approved drug that can prevent the export of E2F7 from the nucleus and thereby restore the efficacy of anthracycline chemotherapy in head and neck cancer.

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