Acquired mutations can induce resistance to hormonal therapy in patients with breast cancer, suggest findings by Merenbakh-Lamin and colleagues. The investigators analysed samples obtained from 13 patients with metastatic breast cancer for mutations in cancer-related genes and identified a mutation in ERα in liver metastases of five patients who developed resistance to hormonal therapy. The primary tumours had not previously harboured this mutation, which structural modelling showed leads to a conformational change in the ligand-binding domain that ultimately alters binding of tamoxifen.
References
Merenbakh-Lamin, K. et al. D538G mutation in estrogen receptor-α: a novel mechanism for acquired endocrine resistance in breast cancer. Cancer Res. 10.1158/0008-5472.CAN-13-1197
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Acquired endocrine resistance in breast cancer. Nat Rev Endocrinol 10, 66 (2014). https://doi.org/10.1038/nrendo.2013.244
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DOI: https://doi.org/10.1038/nrendo.2013.244