PDF(Pubmed)
Abstract：
Tamoxifen is a widely used anti‑estrogen drug in the endocrine therapy of breast cancer (BC). It blocks estrogen signaling by competitively binding to estrogen receptor α (ERα), thereby inhibiting the growth of BC cells. However, with the long‑term application of tamoxifen, a subset of patients with BC have shown resistance to tamoxifen, which leads to low overall survival and progression‑free survival. The molecular mechanism of resistance is mainly due to downregulation of ERα expression and abnormal activation of the PI3K/AKT/mTOR signaling pathway. Moreover, the downregulation of targeted gene expression mediated by DNA methylation is an important regulatory mode to control protein expression. In the present review, methylation and tamoxifen are briefly introduced, followed by a focus on the effect of methylation on tamoxifen resistance and sensitivity. Finally, the clinical application of methylation for tamoxifen is described, including its use as a prognostic indicator. Finally, it is hypothesized that when methylation is used in combination with tamoxifen, it could recover the resistance of tamoxifen.
摘要：
他莫昔芬是乳腺癌（BC）内分泌治疗中广泛使用的抗雌激素药物。它通过竞争性结合雌激素受体α（ERα）来阻断雌激素信号，从而抑制BC细胞的生长。然而,随着他莫昔芬的长期应用，一部分BC患者对他莫昔芬有耐药性，这导致低总生存率和无进展生存率。耐药的分子机制主要是由于ERα表达下调和PI3K/AKT/mTOR信号通路异常激活。此外，DNA甲基化介导的靶向基因表达下调是调控蛋白质表达的重要调控方式。在本次审查中，简要介绍了甲基化和他莫昔芬，其次是甲基化对他莫昔芬耐药性和敏感性的影响。最后,描述了他莫昔芬甲基化的临床应用，包括其作为预后指标的用途。最后,假设当甲基化与他莫昔芬联合使用时，它可以恢复他莫昔芬的抗性。
