Advances in epigenetic mechanism and drug research of reversing resistance to endocrine therapy in breast cancer / 肿瘤

ABSTRACT

Breast cancer is now the most common malignant tumor in Chinese women. Approximately 70% of breast cancers express estrogen receptor (ER) which plays a critical role in the development of breast cancer. Endocrine therapy has become one of the most effective treatments for ER-positive breast cancer. At present, the endocrine therapy drugs are mainly divided into three categories selective ER modulators, selective ER down-regulators and aromatase inhibitors. The adjuvant endocrine therapy with these drugs can reduce the risk of breast cancer recurrence by nearly 40%. However, the resistance of tumor cells to endocrine therapy is a major factor limiting the success of breast cancer treatment. The known mechanisms of endocrine therapy resistance include the concentration of estrogen increased in tumor microenvironment, ER gene mutation, up-regulation of multiple molecular signal pathway, and epigenetic mechanisms. Overcoming endocrine therapy resistance is essential for further improving the benefit rate of endocrine therapy. In this review, the progresses of epigenetic mechanisms (including DNA methylation and histone modification) and epigenetic drugs (including DNAmethyltransferases inhibitors and histone deacetylases inhibitors) of endocrine therapy resistance in ER-positive breast cancer are introduced, in order to further understand the mechanism and therapeutics of endocrine therapy resistance in breast cancer.