HIFs, angiogenesis, and metabolism: elusive enemies in breast cancer

被引：251

作者：

de Heer, Ellen C. ^{[1
]}

Jalving, Mathilde ^{[1
]}

Harris, Adrian L. ^{[2
]}

机构：

[1] Univ Groningen, Univ Med Ctr Groningen, Dept Med Oncol, Groningen, Netherlands

[2] Univ Oxford, Weatherall Inst Mol Med, Mol Oncol Labs, Headley Way, Oxford OX3 9DS, England

来源：

JOURNAL OF CLINICAL INVESTIGATION | 2020年 / 130卷 / 10期

关键词：

HYPOXIA-INDUCIBLE FACTOR; ENDOTHELIAL GROWTH-FACTOR; MOLECULAR-MECHANISMS; C-MET; NEOADJUVANT CHEMOTHERAPY; PROGNOSTIC-SIGNIFICANCE; GLUTAMINE-METABOLISM; CARBONIC-ANHYDRASES; MICROVESSEL DENSITY; 1ST-LINE THERAPY;

D O I：

10.1172/JCI137552

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Hypoxia-inducible factors (HIFs) and the HIF-dependent cancer hallmarks angiogenesis and metabolic rewiring are well-established drivers of breast cancer aggressiveness, therapy resistance, and poor prognosis. Targeting of HIF and its downstream targets in angiogenesis and metabolism has been unsuccessful so far in the breast cancer clinical setting, with major unresolved challenges residing in target selection, development of robust biomarkers for response prediction, and understanding and harnessing of escape mechanisms. This Review discusses the pathophysiological role of HIFs, angiogenesis, and metabolism in breast cancer and the challenges of targeting these features in patients with breast cancer. Rational therapeutic combinations, especially with immunotherapy and endocrine therapy, seem most promising in the clinical exploitation of the intricate interplay of HIFs, angiogenesis, and metabolism in breast cancer cells and the tumor microenvironment.

引用

页码：5074 / 5087

页数：14

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