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摘要
雌激素α-受体活跃 (ER +)的人群中,乳腺癌占70 - 75%的发病率。对于ER +乳腺癌患者,他莫昔芬基于内分泌的治疗已经超过三十年。治疗乳腺癌的年死亡率降低了31%,而且仍是最有效的有针对性的癌症治疗。然而,大约有三分之一的患者治疗辅助他莫昔芬受到的复发性疾病的困扰。,因此,在为这些患者提供有效的治疗方法时,他莫昔芬的耐药性仍然是一个重大的挑战。为了克服这一难题,进行了底层机制强化研究,结果显示复杂因素的识别/途径导致他莫昔芬的耐药性,包括一组网络生长因子受体(FGFR HER2,EGFR,IGF1R) 对ER上调信号的调节,PI3K-PTENER /一种蛋白激酶/ mTOR途径的改变,和NF-κB信号提高。尽管取得了这些进步,我们对获得性耐药的理解依然支离破碎,缺乏一个平台将这些多样化的分子因素/通路整合到一个有凝聚力的机械模型。尽管如此,在细胞水平上,推动癌症转移和治疗抵抗中,癌症干细胞是关键。同样的, 新兴的重要证据是三苯氧胺耐药性对乳腺癌干细胞(BCSCs)的重要作用。在本文中,我们将讨论他莫昔芬耐药性与乳腺癌干细胞(BCSCs)之间的关系和他莫昔芬耐药性在BCSC紧急扩张中分子因素/通路的最新发展。
关键词: 乳腺癌,乳腺癌干细胞,内分泌治疗,雌激素受体,他莫昔芬,他莫昔芬耐药性
Current Medicinal Chemistry
Title:Factors Promoting Tamoxifen Resistance in Breast Cancer via Stimulating Breast Cancer Stem Cell Expansion
Volume: 22 Issue: 19
关键词: 乳腺癌,乳腺癌干细胞,内分泌治疗,雌激素受体,他莫昔芬,他莫昔芬耐药性
摘要: Estrogen receptor-alpha positive (ER+) breast cancer constitutes 70-75% of the disease incidence. Tamoxifen has been the basis of endocrine therapy for patients with ER+ breast cancer for more than three decades. The treatment reduces the annual mortality rate of breast cancer by 31%, and remains the most effective targeted cancer therapy. However, approximately one-third of patients treated with adjuvant tamoxifen suffer from aggressive recurrent disease. Resistance to tamoxifen, thus, remains a major challenge in providing effective treatments for these patients. In an effort to overcome the resistance, intensive research has been conducted to understand the underlying mechanisms; this has resulted in the identification of complex factors/pathways contributing to tamoxifen resistance, including modulations of the ERsignaling, upregulation of a set of growth factor receptor networks (HER2, EGFR, FGFR, and IGF1R), alterations of the PI3K-PTEN/AKT/mTOR pathway, and an elevation of the NF-κB signaling. Despite these advances, our understanding of the acquired resistance remains fragmented and there is a lack of a platform to integrate these diversified molecular factors/ pathways into a cohesive mechanistic model. Nonetheless, at the cellular level, it is becoming increasingly recongnized that cancer stem cells (CSCs) are key in driving cancer metastasis and therapy resistance. Likewise, evidence is emerging for the critical contributions of breast cancer stem cells (BCSCs) to tamoxifen resistance. In this review, we will discuss these recent developments of BCSC-mediated resistance to tamoxifen and the contributions of those demonstrated molecular factors/pathways to BCSC expansion during the emergency of tamoxifen resistance.
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Cite this article as:
Factors Promoting Tamoxifen Resistance in Breast Cancer via Stimulating Breast Cancer Stem Cell Expansion, Current Medicinal Chemistry 2015; 22 (19) . https://dx.doi.org/10.2174/0929867322666150416095744
DOI https://dx.doi.org/10.2174/0929867322666150416095744 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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