Targeting hypoxia-inducible factors for breast cancer therapy: A narrative review

Abstract

Hypoxia-inducible factors (HIFs), central regulators for cells to adapt to low cellular oxygen levels, are often overexpressed and activated in breast cancer. HIFs modulate the primary transcriptional response of downstream pathways and target genes in response to hypoxia, including glycolysis, angiogenesis and metastasis. They can promote the development of breast cancer and are associated with poor prognosis of breast cancer patients by regulating cancer processes closely related to tumor invasion, metastasis and drug resistance. Thus, specific targeting of HIFs may improve the efficiency of cancer therapy. In this review, we summarize the advances in HIF-related molecular mechanisms and clinical and preclinical studies of drugs targeting HIFs in breast cancer. Given the rapid progression in this field and nanotechnology, drug delivery systems (DDSs) for HIF targeting are increasingly being developed. Therefore, we highlight the HIF related DDS, including liposomes, polymers, metal-based or carbon-based nanoparticles.

Hybrid computational modeling highlights reverse warburg effect in breast cancer-associated fibroblasts

“…Already recognized in RA as a driver of inflammation, angiogenesis, and cartilage destruction [70] , targeting HIF-1 has not yet been proposed within a therapeutic strategy aiming at the resolution of metabolic reprogramming in fibroblasts. In BC, therapeutic opportunities targeting HIF-1 appeared until very recently to be limited to its metastatic or driver of tumor-proliferation activity [71] . Growing interest in metabolic targeting to address pro-tumor characteristics resulted in a few insights such as Honokiol as an inhibitor of HIF-1-mediated glycolysis to halt BC cells growth [72] .…”

Targeting Hypoxia-Inducible Factor-1 (HIF-1) in Cancer: Emerging Therapeutic Strategies and Pathway Regulation

“…Its interactions with HIF subunits, co-activators, and co-repressors form a complex gene regulatory network. This intricacy helps cells adapt to the specific demands of their microenvironment [ 9 , 13 ].…”

“…The targeting of HIFs has been recognized as a prospective strategy for enhancing cancer therapies [ 8 , 9 , 10 ]. A number of small molecular inhibitors targeting HIF have been developed and incorporated into various drug delivery systems.…”

Biomimetic liposomal nanozymes improve breast cancer chemotherapy with enhanced penetration and alleviated hypoxia

“…Elleviating hypoxia could be a potential strategy to solve the challenge. Many therapeutic strategies for breast cancer hypoxia were reported including HIF inhibitors [ 12 ], hypoxia-activable prodrug [ 13 ] and in situ oxygenating to modulate TME [ 14 ]. Usually, there two main approaches for normalizing tumor oxygen supply.…”