eIF4A controls translation of estrogen receptor alpha and is a therapeutic target in advanced breast cancer

What is it about?

In this article, we report that the expression of the estrogen receptor (ER) protein requires the helicase eIF4A and that an eIF4A inhibitor reduces ER levels and blocks the growth of breast cancer cell growth. The drug works on WT ER but also on ER mutants that are resistant to ER inhibitors. Combining the drug with a drug that causes ER degradation has synergistic effects on ER expression and antitumor activity. In this publication we describe a new type of ER inhibitor which can work in patients whose tumors are resistant to known anti-estrogens.

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Why is it important?

The majority of breast cancers are estrogen dependent and can be treated with modalities that inhibit ER but almost all patients develop resistance. Our strategy inhibits ER in resistant tumors. In a phase 1 trial in patients who are resistant to multiple treatment modalities including ER and cdk4 inhibitors, combined inhibition of eIF4A and induces of ER degradation has caused remarkable responses and addition of a cdk4 inhibitor enhanced activity. The most surprising result is that the combination had little or no toxicity. Thus, we report a novel way to inhibit ER and a potentially useful way to treat resistant, metastatic breast cancer.