The Fight Against Tamoxifen Resistance in Breast Cancer Therapy: A New Target in the Battle?

Treatments for ER⁺ breast cancer and chemoprevention that target specific domains of the estrogen receptor. Estradiol activates estrogenic growth signals after binding the estrogen receptor. Two major classes of compounds are used in breast cancer therapy to inhibit ER growth signals. The aromatase inhibitors (AIs) inhibit the enzyme responsible for production of estradiol from androgenic precursors. Selective estrogen receptor modulators (SERMs) compete with estradiol for binding to the ligand binding domain and alter the activator or repressor proteins that subsequently bind. Disulfide benzamide (DIBA) acts in a novel way, by interrupting the second zinc finger of the DNA binding domain, preventing receptor interaction at EREs.