Cancer cell respiration: Hypoxia and pH in solid tumors

Abstract

Tumor cells require large amounts of oxygen and nutrients for rapid proliferation. Blood vessel growth is not fast enough to meet these requirements, however, resulting in low oxygen and glucose concentrations in tumor tissues. Tumor hypoxia is closely related to increased levels of glycolysis and in turn accumulation of lactate in the tissue. Therefore, tumor tissue pH decreases in the hypoxic tumors. Gene expression profiles in tumor tissues change in hypoxic environments in order to adapt to the acidic conditions. These genes are involved in angiogenesis, cell growth, apoptosis, and glycolysis. Gene induction is primarily controlled at the level of transcription by hypoxia-inducible factor-1 (HIF-1). HIF-1α is stabilized under hypoxic conditions and forms a heterodimer with HIF-1β. HIF-1 then binds to a hypoxia response element (HRE) within a hypoxia-specific promoter for gene expression. Tumor-specific drug and gene delivery systems have been developed using hypoxia-inducible regulation systems. In this chapter, strategies for pH-specific drug delivery and gene therapy in hypoxic tumors are described.