Weakened binding of tamoxifen to critical amino acid residues on the estrogen receptor as a potential driver of uterine cancer

Breast cancer remains the most common cancer among women, and in a significant number of cases its progression is due to the influence of estrogen receptors. Tamoxifen, being a selective estrogen receptor modulator, is widely used in adjuvant therapy, especially in premenopausal women. However, its use is associated with an increased risk of endometrial cancer, which limits its use. In this study, molecular dynamics simulations of tamoxifen and raloxifene complexes with estrogen receptor alpha were performed. The analysis focused on interactions with critical amino acid residues within the receptor’s active site. The results indicate that weakened binding of tamoxifen to these residues may underlie its association with ER-dependent uterine cancer.