Hypoxia signaling in cancer: Implications for therapeutic interventions

Abstract

Hypoxia is a persistent physiological feature of many different solid tumors and a key driver of malignancy, and in recent years, it has been recognized as an important target for cancer therapy. Hypoxia occurs in the majority of solid tumors due to a poor vascular oxygen supply that is not sufficient to meet the needs of rapidly proliferating cancer cells. A hypoxic tumor microenvironment (TME) can reduce the effectiveness of other tumor therapies, such as radiotherapy, chemotherapy, and immunotherapy. In this review, we discuss the critical role of hypoxia in tumor development, including tumor metabolism, tumor immunity, and tumor angiogenesis. The treatment methods for hypoxic TME are summarized, including hypoxia‐targeted therapy and improving oxygenation by alleviating tumor hypoxia itself. Hyperoxia therapy can be used to improve tissue oxygen partial pressure and relieve tumor hypoxia. We focus on the underlying mechanisms of hyperoxia and their impact on current cancer therapies and discuss the prospects of hyperoxia therapy in cancer treatment.

Hypoxia‐activated ADCC‐enhanced humanized anti‐CD147 antibody for liver cancer imaging and targeted therapy with improved selectivity

“…Such minor decrease suggested that although Ab-PEGylation provided desirable shield for removing nonspecific binding, its affinity to CD147 Ag also decreased slightly. This result is consistent with previous observations, 18,48 and site-specific PEGylation may be considered in the future. Two limitations exist in this study.…”

“…These microenvironmental features are distinct from those of normal tissues and can trigger specific chemical reactions. Hypoxic tumor microenvironment has been exploited to design stimuli‐responsive prodrugs or nanodrugs 15–18 . Hypoxic cells produce 100–1000 times more nitroreductase than normoxic cells, which can reduce azobenzene (azo)‐containing drugs for conditional release 19–21 .…”

Therapeutic Potential of Tumor Metabolic Reprogramming in Triple-Negative Breast Cancer

“…In the hypoxic tumor microenvironment, HIF-1α is activated through the mTOR (mammalian target of rapamycin), NF-κB (nuclear factor kappa B), and JAK (Janus kinase)-STAT signaling pathways by receptors on the plasma membrane (e.g., TCR-T cell receptor, GFR-growth factor receptor, IL-6R and TLR-Toll-like receptor) [ 71 ]. Upregulated HIF-1α combines with HIF-1β to form a dimer in the nucleus.…”

Tumour hypoxia sensor: A state of the art in oral cancer liquid biopsy

“…Identifying it promptly allows targeted therapies to address hypoxia-related aggressiveness, potentially curbing tumour progression and bettering patient outcomes. 7 While various methods detect tumour hypoxia, each bears limitations. Polarographic oxygen electrodes, the gold standard for accuracy, remain invasive and impractical for clinical use.…”

“…Early detection of hypoxia in cancer is pivotal, guiding tailored treatments for enhanced efficacy. Identifying it promptly allows targeted therapies to address hypoxia‐related aggressiveness, potentially curbing tumour progression and bettering patient outcomes 7 . While various methods detect tumour hypoxia, each bears limitations.…”