ESR1 fusions and therapeutic resistance in metastatic breast cancer.
ESR1 fusions and therapeutic resistance in metastatic breast cancer.
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DOI：
10.3389/fonc.2022.1037531
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发表时间：
2022
影响因子：
4.7
通讯作者：
中科院分区：
文献类型：
--
作者：
乳腺癌是女性最常见的恶性肿瘤，也是全球女性癌症死亡的主要原因。乳腺癌的最常见亚型是表达雌激素受体（ER）的激素受体阳性。用内分泌疗法（ET）靶向ER是ER阳性（ER+）乳腺癌的当前护理标准，在早期疾病中将死亡率降低高达40%。然而，对ET的耐药性代表了ER+乳腺癌患者的主要临床挑战，导致疾病复发或转移性疾病进展。ET抗性的显著驱动因素是ER基因（ESR1）中的错义突变，导致组成型转录活性和ET敏感性降低。这些突变在转移性乳腺癌（MBC）中特别突出和有害。除了激活ESR1点突变外，新出现的证据表明，涉及ESR1基因的染色体易位也可以通过形成具有组成性转录活性的嵌合转录因子来驱动ET抗性。虽然这些ESR1基因融合是相对罕见的，但它们在ET耐药转移性疾病中富集。本文综述了ER融合蛋白的特点及其与侵袭性和转移性乳腺癌临床结局的关系。并对ER融合蛋白的结构、功能和临床意义进行了分类。最后，本文综述了ER融合蛋白的转移表型及其在内源性ET抵抗中的作用。
Breast cancer is the most frequent female malignant tumor, and the leading cause of cancer death in women worldwide. The most common subtype of breast cancer is hormone receptor positive that expresses the estrogen receptor (ER). Targeting ER with endocrine therapy (ET) is the current standard of care for ER positive (ER+) breast cancer, reducing mortality by up to 40% in early- stage disease. However, resistance to ET represents a major clinical challenge for ER+ breast cancer patients leading to disease recurrence or progression of metastatic disease. Salient drivers of ET resistance are missense mutations in the ER gene (ESR1) leading to constitutive transcriptional activity and reduced ET sensitivity. These mutations are particularly prominent and deleterious in metastatic breast cancer (MBC). In addition to activating ESR1 point mutations, emerging evidence imposes that chromosomal translocation involving the ESR1 gene can also drive ET resistance through the formation of chimeric transcription factors with constitutive transcriptional activity. Although these ESR1 gene fusions are relatively rare, they are enriched in ET resistant metastatic disease. This review discusses the characteristics of ER fusion proteins and their association with clinical outcomes in more aggressive and metastatic breast cancer. The structure and classification of ER fusion proteins based on function and clinical significance are also addressed. Finally, this review summarizes the metastatic phenotypes exhibited by the ER fusion proteins and their role in intrinsic ET resistance.
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影响因子：
8
作者：
Browne AL;Charmsaz S;Varešlija D;Fagan A;Cosgrove N;Cocchiglia S;Purcell S;Ward E;Bane F;Hudson L;Hill AD;Carroll JS;Redmond AM;Young LS
通讯作者：
Young LS
影响因子：
3.2
作者：
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通讯作者：
Satolli, Maria Antonietta
DOI：
10.1016/j.bbrc.2017.01.012
发表时间：
2017-02-05
影响因子：
3.1
作者：
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Shen, Ching-Ju
影响因子：
5.9
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通讯作者：
Germain D
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17.1
作者：
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通讯作者：
Arteaga CL