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靶向乳腺癌中的肿瘤缺氧

Targeting tumour hypoxia in breast cancer.

作者信息

Milani Manuela, Harris Adrian L

机构信息

Department of Medical Oncology, University of Oxford, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK.

出版信息

Eur J Cancer. 2008 Dec;44(18):2766-73. doi: 10.1016/j.ejca.2008.09.025. Epub 2008 Nov 5.

Abstract

Breast cancer is the most common malignancy in women. Hypoxia occurs in breast cancer and in other solid tumours due to the tumour outgrowing the existing vasculature. Hypoxia leads to an adaptive response, orchestrated by HIF-1 (hypoxia-inducible factor-1), that is crucial for tumour progression and therapy resistance responsible for poor patient outcome. In several studies, downstream targets of HIF-1alpha were considered as hypoxia markers. The biological heterogeneity of breast cancer has been investigated through genome profiling technologies. The recent data suggest that treatment outcome depends on individual genetic features and that the hypoxia signature is a significant prognostic factor. The identification of molecular biomarkers with the potential to predict treatment outcome is essential for selecting patients to receive the most beneficial therapy, and in the future may drive stratification in clinical trials.

摘要

乳腺癌是女性中最常见的恶性肿瘤。由于肿瘤生长超过现有脉管系统,乳腺癌及其他实体瘤中会出现缺氧情况。缺氧会引发由缺氧诱导因子-1(HIF-1)精心调控的适应性反应,这对肿瘤进展和治疗抵抗至关重要,而治疗抵抗会导致患者预后不良。在多项研究中,HIF-1α的下游靶点被视为缺氧标志物。通过基因组分析技术对乳腺癌的生物学异质性进行了研究。近期数据表明,治疗结果取决于个体遗传特征,且缺氧特征是一个重要的预后因素。识别具有预测治疗结果潜力的分子生物标志物对于选择能接受最有益治疗的患者至关重要,并且在未来可能推动临床试验中的分层。

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