Endocrine-resistant breast cancer: underlying mechanisms and strategies for overcoming resistance.
Endocrine-resistant breast cancer: underlying mechanisms and strategies for overcoming resistance.
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DOI：
10.1007/bf02967635
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发表时间：
2003-01-01
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影响因子：
--
通讯作者：
Kurebayashi, Junichi
中科院分区：
文献类型：
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作者：
Kurebayashi, Junichi
雌激素在乳腺癌的发生、发展中起重要作用。然而，三分之一的乳腺癌对内分泌治疗没有反应，大多数内分泌反应性乳腺癌随后对内分泌治疗产生耐药性。为了阐明乳腺癌内分泌抵抗的发生机制，人们付出了巨大的努力。由于乳腺癌中雌激素的主要靶分子是雌激素受体（ER）-α，因此大多数研究都集中在研究内分泌抵抗性乳腺癌中ER-α的定量和定性变化。不表达ER-α的乳腺癌对内分泌治疗无效。一些表达ER-α的乳腺癌对内分泌治疗也没有反应，大多数具有获得性内分泌抵抗的乳腺癌保留ER-α表达，这表明乳腺癌细胞中ER-α的消失不是对内分泌治疗抵抗的常见原因。最近的分子生物学研究表明，定性和功能变化，如基因突变和ER-α的磷酸化，导致乳腺癌的内分泌抵抗。此外，有研究表明，乳腺癌组织中的表观遗传变化（如缺氧）可诱导内分泌抵抗。了解内分泌抵抗的确切机制可能使临床医生能够制定新的策略来延缓或克服乳腺癌的内分泌抵抗。
Estrogen plays important roles in the development and progression of breast cancer. However, one-third of breast cancers fail to respond to endocrine therapy and most endocrine-responsive breast cancers subsequently become resistant to endocrine therapy. A tremendous effort has been made to elucidate the mechanisms responsible for the development of endocrine-resistance in breast cancer. Since the main target molecule of estrogen in breast cancer is estrogen receptor (ER)-alpha, most studies have focused on investigating quantitative and qualitative changes in ER-alpha in endocrine-resistant breast cancer. Breast cancers expressing no ER-alpha fail to respond to endocrine therapy. Some breast cancers expressing ER-alpha also fail to respond to endocrine therapy and most breast cancers with acquired endocrine resistance retain ER-alpha expression, which suggests that the disappearance of ER-alpha in breast cancer cells is not a common cause of resistance to endocrine therapy. Recent molecular biological studies have shown evidence that qualitative and functional changes, such as gene mutations and phosphorylation of ER-alpha, cause endocrine resistance in breast cancer. In addition, it has been suggested that endocrine resistance could be induced by epigenetic changes, such as hypoxia, in breast cancer tissues. Understanding the precise mechanisms that underlie endocrine resistance may enable clinicians to develop new strategies for retarding or overcoming endocrine resistance in breast cancer.