HIF-1 transactivates genes encoding proteins that are involved in key aspects of the cancer phenotype, including cell immortalization and de-differentiation, stem cell maintenance, genetic instability, glucose uptake and metabolism, pH regulation, autocrine growth/survival, angiogenesis, invasion/metastasis, and resistance to chemotherapy.
HIF-1/HRE pathway is a promising target for the imaging and the treatment of intractable malignancy (HIF-1; hypoxia-inducible factor 1, HRE; hypoxia-responsive element).
HIF-1 (hypoxia-inducible factor-1) regulates the expression of ~100 genes involved in angiogenesis, metastasis, tumor growth, chemoresistance and radioresistance, underscoring the growing interest in targeting HIF-1 for cancer control.
HIF-1 is a promising target in cancer drug development to increase the patient's response to chemotherapy and radiotherapy as well as the survival rate of cancer patients.
HIF-1 is regarded as a promising target for the drugs used in cancer chemotherapy, and creating readily accessible templates for the development of synthetic drug candidates that could inhibit HIF-1 transcriptional activity is an important pursuit.
Although alterations in each of these processes have been associated with SETD2 loss, the relative role of each in the development of cancer is not fully understood.
Although many of the HIF inhibitors reviewed in this patent survey possess inhibitory activity against cancer and HIF-related diseases, the compounds are still in the early stages of development, most likely due to the complexity of the HIF-1 pathway and their different mechanisms of action for HIF inhibition.
Among iron-dependent dioxygenases, important targets for stimulation by vitamin C in cancer include prolyl hydroxylases targeting the hypoxia-inducible factors HIF-1/HIF-2 and histone and DNA demethylases.
An understanding of underlying mechanisms involved in the activation of HIF-1 in response to both hypoxic stress and oncogenic signals has important implications for how these processes may become deregulated in human cancer.
As NSD1 and SETD2 are known tumor suppressors and loss of H4K20 trimethylation is an early event in cancer progression, which contributes to genomic instability, we propose DMAPT as a potent pharmacologic agent that can reverse NF-κB-dependent and -independent cancer-specific epigenetic abnormalities.
Ascorbate can moderate HIF-1 activity in vitro and is associated with HIF pathway activation in a number of cancer types, but whether tissue ascorbate levels influence the HIF pathway in breast cancer is unknown.
Because HIF-1 is a major positive contributor in human tumorigenesis and angiogenesis, we believe that its inhibition by 1,25(OH)(2)D(3) strengthens the rationale to use vitamin D and its low-calcemic analogues in cancer chemoprevention and therapy.
Carbonic anhydrase 9 (CA9), which is induced by hypoxia-inducible factor 1 (HIF1) in response to hypoxia, is overexpressed in many types of cancer including renal cell carcinoma (RCC).
Cetuximab inhibits HIF-1-regulated glycolysis in cancer cells, thereby reversing the Warburg effect and leading to inhibition of cancer cell metabolism.
Clinically, hypoxia and the hypoxia inducible transcription factors HIF-1 and HIF-2 are associated with cancer stem cells, metastasis and drug resistance in multiple tumor types.
Considering the important contributions of HIF-1 in angiogenesis and vasculogenesis, it should be considered a promising target for treating ischaemic diseases or cancer.
Despite significant similarities, HIF1 (HIF1α/ARNT) and HIF2 (HIF2α/ARNT) activate common as well as unique target genes and exhibit different functions in cancer biology.