Novel Agents Aimed at Disrupting Cancer Metabolism Gain Ground

Jenna Bassett, PhD
Published: Friday, Jan 25, 2019
Almost a century ago, Otto Warburg, MD, PhD, demonstrated that cancer cells prefer to obtain energy via glycolysis, taking in large amounts of glucose and producing lactic acid at high levels, even in the presence of oxygen and healthy mitochondria.1

Figure 1. Differences in the Process of Glycolysis

Figure 1. Differences in the Process of Glycolysis Despite its importance, the mechanisms behind the Warburg effect are not well understood. Nevertheless, due to its presence in a wide range of cancers, the Warburg effect has become an intriguing target for anticancer therapeutics. Although most antitumor therapies are designed to treat a specific cancer type, therapeutics that target the Warburg effect have the potential to treat a broad range of cancers.

The development of these types of therapies has the potential to provide broad-range treatment with minimal adverse effects, leading to better patient care and favorable outcomes.

The Warburg Effect and Cancer Metabolism

Glycolysis is a stage of cellular respiration through which glucose is converted into growth and survival.6 It has since been established that malignant cells reprogram their metabolic pathways to support uncontrolled cell growth, maintaining oxidative phosphorylation processes while ramping up glycolysis. Several hypotheses exist to explain the pyruvate to release energy in the form of ATP. Although aerobic glycolysis is less efficient than oxidative phosphorylation, producing fewer molecules of ATP per unit of glucose, malignant cells may favor it because the process can be executed significantly faster.3 Cancer cells that favor glycolysis can quickly generate energy by increasing glucose uptake. Increased uptake results in an increase in glycolytic rate, facilitating the generation of ATP that can meet the demands of uncontrolled cell growth.
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