Inserm, EHESP, Irset (Institut de Recherche en Santé, Environnement et Travail)-UMR_S1085, Rennes University, F-35000 Rennes, France.
Int J Mol Sci. 2021 Jan 13;22(2):756. doi: 10.3390/ijms22020756.
Breast cancer (BC) is the most common cancer among women worldwide. More than 70% of BC cases express estrogen receptor alpha (ERα), a central transcription factor that stimulates the proliferation of breast cancer cells, usually in the presence of estrogen. While most cases of ER-positive BC initially respond to antiestrogen therapies, a high percentage of cases develop resistance to treatment over time. The recent discovery of mutated forms of ERα that result in constitutively active forms of the receptor in the metastatic-resistance stage of BC has provided a strong rationale for the development of new antiestrogens. These molecules targeting clinically relevant ERα mutants and a combination with other pharmacological inhibitors of specific pathways may constitute alternative treatments to improve clinical practice in the fight against metastatic-resistant ER-positive BC. In this review, we summarize the latest advances regarding the particular involvement of point mutations of ERα in endocrine resistance. We also discuss the involvement of synonymous ERα mutations with respect to co-translational folding of the receptor and ribosome biogenesis in breast carcinogenesis.
乳腺癌（BC）是全球女性中最常见的癌症。超过 70%的 BC 病例表达雌激素受体 alpha（ERα），这是一种中央转录因子，可刺激乳腺癌细胞的增殖，通常在雌激素存在的情况下。虽然大多数 ER 阳性 BC 病例最初对抗雌激素治疗有反应，但随着时间的推移，很大一部分病例会对治疗产生耐药性。最近发现 ERα 的突变形式导致受体在转移性耐药阶段处于持续激活状态，这为开发新的抗雌激素提供了强有力的依据。这些针对临床相关 ERα 突变体的分子与特定途径的其他药理学抑制剂联合使用，可能构成改善针对转移性耐药 ER 阳性 BC 的临床实践的替代治疗方法。在这篇综述中，我们总结了 ERα 点突变在内分泌耐药中的最新进展。我们还讨论了同义 ERα 突变与受体共翻译折叠和核糖体生物发生在乳腺癌发生中的关系。
