New insight into breast cancer resistance to hormone therapy

An international team of researchers led by scientists at Baylor College of Medicine has new insights into the function of neurofibromin, a tumor suppressor produced by the NF1 gene. It is well known that neurofibromin keeps cancer growth in check by repressing the activity of a cancer driver called Ras. The new research reveals a previously unknown function of neurofibromin – directly repressing gene expression controlled by the estrogen receptor-α (ER). Thus, when neurofibromin is lost, Ras and ER functions are both activated, causing treatment resistance and metastasis for ER+ breast cancer.

These findings, appearing in Cancer Cell, suggest that a therapeutic approach must combine two different drugs, a SERD (e.g., fulvestrant) to degrade ER and a MEK inhibitor (e.g., selumetinib or binimetinib) to inhibit Ras downstream signaling, in order to effectively treat neurofibromin-depleted ER+ breast cancer. When this combination therapy was tested in animal models, the result was tumor regression. The next step is to begin clinical trials of the effectiveness of this therapeutic approach in patients.

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