Editorial: How Do Metabolism, Angiogenesis, and Hypoxia Modulate Resistance? (original) (raw)

Frontiers in Oncology

Abstract

Metabolic alterations were among the first discovered hallmarks of cancer. They were first described 90 years ago when Otto Warburg realized that cancer cells in culture had a relatively increased metabolic rate (the Warburg hypothesis). It has been proposed that the drastic changes seen in cancer metabolism are in part attributed to mutations in the mtDNA, metabolic reprogramming, or mitochondrial dysfunction. However, novel players in cancer metabolism are emerging. In this regard, the review of Fernández et al. describes how lipidic alterations impact cancer prognosis and response to treatment. For example, it has been described that obesity increases the risk of cancer death, possibly due to the consequences of lipid accumulation throughout a lifetime. Lipid accumulation changes the microenvironment and produces chronic inflammation by increasing several cytokines. While the levels of genetic or epigenetic modifications diverge in different cancer types, all cancer cells adapt to drastic microenvironmental conditions. This adaptation entails metabolic reprogramming to cope with scarce nutrients and oxygen. Lipid metabolism sustains cancer initiation and contributes to cancer progression and therapy resistance. The role of lipids has been underestimated, as they have largely been considered scaffolds of biological membranes. In recent decades, the role of lipids in cancer has emerged in parallel to the characterization of lipids as essential components of cell signaling, redox homeostasis control, and energy sources (i.e., ß-fatty acid oxidation). Moreover, while de novo synthesis of fatty acids and cholesterol is restricted to the liver and adipocytes in normal cells, cancer cells can synthesize such components. This altered lipid metabolism affects key steps involved in the metastatic process, like migration, invasion, and angiogenesis, and can also be associated with prognosis. Moreover, Fernández et al. provide a list of preclinical and clinical studies with bioactive compounds from natural sources to target lipid metabolism and associated risk factors in cancer. Tumor adaptation to hypoxia is another important aspect that modulates resistance in cancer. Hypoxia is a forced situation where oxygen levels are different from normal physiological conditions. Hypoxia occurs in higher or minor levels in most cancers, if not all. The detection of hypoxic areas by clinical imaging would improve cancer chemotherapeutic treatments and optimal radiotherapy planning. The technique of positron emission tomography (PET) measures cancer metabolism and cellular proliferation, but it can also measure blood flow and oxygen use. PET can

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