Current advances in biomarkers for targeted therapy in triple-negative breast cancer.
Current advances in biomarkers for targeted therapy in triple-negative breast cancer.
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DOI：
10.2147/bctt.s114659
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Ait-Oudhia S
中科院分区：
文献类型：
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作者：
Fleisher B;Clarke C;Ait-Oudhia S
三阴性乳腺癌（TNBC）是一种复杂的异质性疾病，其特征在于缺乏三种标志性受体：人表皮生长因子受体2、雌激素受体和孕激素受体。与其他乳腺癌亚型相比，TNBC更具侵略性，在非洲裔美国人中的患病率更高，并且更频繁地影响年轻患者。目前，TNBC缺乏用于定制治疗的临床上可接受的靶标，从而不需要候选生物标志物。BiomarkerBase是一个用于寻找临床试验中报告的生物标志物的在线平台，用于筛选TNBC的所有潜在生物标志物，并仅选择通过clinicaltrials.gov在已完成的TNBC试验中注册的生物标志物。所选候选生物标志物被分类为替代，预后，预测或药效学（PD），并按血液中，细胞表面，细胞质或细胞核中的位置进行组织。血液生物标志物包括血管内皮生长因子/血管内皮生长因子受体和白细胞介素-8（IL-8）;细胞表面生物标志物包括EGFR、胰岛素样生长因子结合蛋白、c-Kit、c-Met和PD-L1;细胞质生物标志物包括PIK 3CA、pAKT/S6/p4 E-BP 1、PTEN、ALDH 1和PIK 3CA/AKT/mTOR相关代谢物;细胞核生物标志物包括BRCA 1、糖皮质激素受体、TP 53和Ki 67。候选生物标志物被进一步组织成展示潜在连接性的“细胞蛋白质网络”。这篇综述为TNBC突破性靶向治疗的有前景的生物标志物提供了一个清单和参考点。
Triple-negative breast cancer (TNBC) is a complex heterogeneous disease characterized by the absence of three hallmark receptors: human epidermal growth factor receptor 2, estrogen receptor, and progesterone receptor. Compared to other breast cancer subtypes, TNBC is more aggressive, has a higher prevalence in African-Americans, and more frequently affects younger patients. Currently, TNBC lacks clinically accepted targets for tailored therapy, warranting the need for candidate biomarkers. BiomarkerBase, an online platform used to find biomarkers reported in clinical trials, was utilized to screen all potential biomarkers for TNBC and select only the ones registered in completed TNBC trials through clinicaltrials.gov. The selected candidate biomarkers were classified as surrogate, prognostic, predictive, or pharmacodynamic (PD) and organized by location in the blood, on the cell surface, in the cytoplasm, or in the nucleus. Blood biomarkers include vascular endothelial growth factor/vascular endothelial growth factor receptor and interleukin-8 (IL-8); cell surface biomarkers include EGFR, insulin-like growth factor binding protein, c-Kit, c-Met, and PD-L1; cytoplasm biomarkers include PIK3CA, pAKT/S6/p4E-BP1, PTEN, ALDH1, and the PIK3CA/AKT/mTOR-related metabolites; and nucleus biomarkers include BRCA1, the gluco-corticoid receptor, TP53, and Ki67. Candidate biomarkers were further organized into a “cellular protein network” that demonstrates potential connectivity. This review provides an inventory and reference point for promising biomarkers for breakthrough targeted therapies in TNBC.