Effects of hypoxia on tumor metabolism

Abstract

A major feature of solid tumors is hypoxia which affects cancer biology, increases resistance to treatment and patient
prognosis. Adaptive responses of cells to hypoxia include stimulation of angiogenesis, erythropoiesis and alteration
of cellular metabolism. Cancer cells are characterized by reprogramming of metabolism leading to increased glycolysis,
attenuation of oxidative phosphorylation and de novo synthesis of fatty acids. Hypoxia-induced activation of
hypoxia-inducible factor (HIF-1) plays an important role in the reprogramming of cancer metabolism by activating
transcription of genes encoding glucose transporters and glycolytic enzymes leading to increased glucose uptake,
and pyruvate dehydrogenase kinase 1 (PDK1), which diminished mitochondrial respiration. The shift from oxidative
to glycolytic metabolism allows maintenance of redox homeostasis, survival and continued proliferation of cancer
cells under hypoxic conditions.