Treatment of choice for squamous cell carcinoma in anus
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Targeting the Metabolic Microenvironment of Tumors
The observation of aerobic glycolysis by tumor cells in by Otto Warburg, and subsequent innovation of imaging glucose uptake by tumors in patients with PET-CT has incited a renewed interest in the altered metabolism of tumors. In normal tissues, these responses mitigate hypoxic stress and induce neo-angiogenesis. In tumors, these pathways are dysregulated and lead to decreased perfusion and exacerbation of hypoxia as a result of immature and chaotic blood vessels. Hypoxia selects for a glycolytic phenotype and resultant acidification of the tumor microenvironment, facilitated by upregulation of proton transporters. Acidification selects for enhanced metastatic potential and reduced drug efficacy through ion trapping. In this review, we provide a comprehensive summary of pre-clinical and clinical drugs under development for targeting aerobic glycolysis, acidosis, hypoxia and hypoxia-response pathways.