The efficacies of therapies targeting key genes, like the estrogen receptor (ER), human epithelial growth factor receptor 2 (HER2/ERBB2), the mammalian target of rapamycin (mTOR) and the epidermal growth factor receptor (EGFR), were influenced by the heterogeneous cancer cells and tumor-associated cells which were characterized by diverse transcriptional or mutational states3–5. The gene discussed is ESR1; the disease is cancer.