Hypoxia in Breast Cancer—Scientific Translation to Therapeutic and Diagnostic Clinical Applications

Ying Zhang,Minghong Wang,Ewelina Biskup,Thomas Schmid,Yuan Huang,Zhaochen Xin,Lora Kozhuharova,Wai-Kin Yu,Fengfeng Cai,Hongyi Zhang

doi:10.3389/fonc.2021.652266

Abstract

Breast cancer has been the leading cause of female cancer deaths for decades. Intratumoral hypoxia, mainly caused by structural and functional abnormalities in microvasculature, is often associated with a more aggressive phenotype, increased risk of metastasis and resistance to anti-malignancy treatments. The response of cancer cells to hypoxia is ascribed to hypoxia-inducible factors (HIFs) that activate the transcription of a large battery of genes encoding proteins promoting primary tumor vascularization and growth, stromal cell recruitment, extracellular matrix remodeling, cell motility, local tissue invasion, metastasis, and maintenance of the cancer stem cell properties. In this review, we summarized the role of hypoxia specifically in breast cancer, discuss the prognostic and predictive value of hypoxia factors, potential links of hypoxia and endocrine resistance, cancer hypoxia measurements, further involved mechanisms, clinical application of hypoxia-related treatments and open questions.

Highlights

Breast cancer has been the most commonly diagnosed cancer and the leading cause of cancer deaths among women, accounting for ∼630,000 deaths in 2018 [1]
The response of cancer cells to hypoxia is ascribed to hypoxia-inducible factors (HIFs) that activate the transcription of a large battery of genes encoding proteins promoting primary tumor vascularization and growth, stromal cell recruitment, extracellular matrix remodeling, cell motility, local tissue invasion, metastasis, and maintenance of the cancer stem cell properties
We summarized the role of hypoxia in breast cancer, discuss the prognostic and predictive value of hypoxia factors, potential links of hypoxia and endocrine resistance, cancer hypoxia measurements, further involved mechanisms, clinical application of hypoxia-related treatments and open questions

Summary

Introduction

Breast cancer has been the most commonly diagnosed cancer and the leading cause of cancer deaths among women, accounting for ∼630,000 deaths in 2018 [1]. The response of cancer cells to hypoxia is ascribed to hypoxia-inducible factors (HIFs) that activate the transcription of a large battery of genes encoding proteins promoting primary tumor vascularization and growth, stromal cell recruitment, extracellular matrix remodeling, cell motility, local tissue invasion, metastasis, and maintenance of the cancer stem cell properties. Intra-tumoral hypoxia increases the number of breast cancer stem cells (BCSCs), which are essential for disease progression and recurrence [8, 17].

Results

Conclusion