Linking EMT programmes to normal and neoplastic epithelial stem cells. Radiation damage to tumor vasculature initiates a program that promotes tumor recurrences. Single-dose radiotherapy disables tumor cell homologous recombination via ischemia/reperfusion injury. The two faces of reactive oxygen species in cancer. Hypoxia-inducible factors: coupling glucose metabolism and redox regulation with induction of the breast cancer stem cell phenotype. Causes, consequences, and therapy of tumors acidosis. Immunity, hypoxia, and metabolism-the menage a trois of cancer: Implications for immunotherapy. The von Hippel-Lindau tumor suppressor protein and clear cell renal carcinoma. Succinate dehydrogenase and fumarate hydratase: linking mitochondrial dysfunction and cancer. Hypoxia induces rapid changes to histone methylation and reprograms chromatin. Tumour hypoxia causes DNA hypermethylation by reducing TET activity. 2-Oxoglutarate-dependent dioxygenases in cancer.
Cellular adaptation to hypoxia through hypoxia inducible factors and beyond. Individual patient data meta-analysis of FMISO and FAZA hypoxia PET scans from head and neck cancer patients undergoing definitive radio-chemotherapy. Prognostic value of tumor oxygenation in 397 head and neck tumors after primary radiation therapy. Lost in application: measuring hypoxia for radiotherapy optimisation. Divergent mutational processes distinguish hypoxic and normoxic tumours. Molecular landmarks of tumor hypoxia across cancer types. Direct measurement of local oxygen concentration in the bone marrow of live animals. Evidence that hypoxia markers detect oxygen gradients in liver: pimonidazole and retrograde perfusion of rat liver. Detection and characterization of tumor hypoxia using pO2 histography. Both of these responses to treatment-induced hypoxia can be targeted therapeutically. New evidence demonstrates that suppression of O 2 consumption using inhibitors of the mitochondrial electron transport chain can relieve tumour hypoxia in patients.Īnticancer therapies that induce vascular damage can exacerbate tumour hypoxia, triggering a vascular repair process that supports tumour regrowth while also suppressing homology-directed repair of DNA damage.
Hypoxia and associated features of the tumour microenvironment (adenosine, acidosis and nutrient deficiencies) are profoundly immunosuppressive agents that alleviate hypoxia and/or acidosis can enhance the efficacy of immune-checkpoint inhibitors. Hypoxia-activated prodrugs have been widely investigated for targeting hypoxic tumour cells, but their clinical development has been compromised by a failure to assess hypoxia (and other relevant biomarkers) in individual tumours.Įlectron-affinic radiosensitizers mimic some of the effects of O 2 in radiation biology and might have applications in highly hypofractionated radiotherapy protocols that are increasingly used to control oligometastatic disease.
O 2 deficiency (euhypoxia), and mutations that have similar effects on patterns of gene expression (pseudohypoxia), have widespread effects on tumour evolution and sensitivity to anticancer agents. This Review provides a perspective on advances at the interface between these two aspects of the TME, with a focus on translational therapeutic opportunities relating to the elimination and/or exploitation of tumour hypoxia. Over the past decade, strong links have been established between these two themes, providing new insights into fundamental aspects of tumour biology and presenting new strategies for addressing the effects of hypoxia and other microenvironmental features that arise from the inefficient microvascular system in solid tumours. The other has focused on cellular interactions involving tumour and non-tumour cells within the TME. One has focused on physicochemical gradients of oxygen, pH and nutrients in the tumour interstitium, motivated in part by the barrier that hypoxia poses to effective radiotherapy. Historically, two different tumour microenvironment (TME) research communities have been discernible. Hypoxia is prevalent in human tumours and contributes to microenvironments that shape cancer evolution and adversely affect therapeutic outcomes.
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