Revisiting the Warburg effect in cancer cells with proteomics. The emergence of new approaches to diagnosis, prognosis and therapy.

Most cancer cells exhibit elevated levels of glycolysis and this metabolic pathway seems to be related to a greater glucose uptake. This phenomenon, known as the Warburg effect, is considered one of the most fundamental metabolic alterations during malignant transformation. Originally, Warburg hypothesised that the aerobic glycolysis of cancer cells could be just an aspect of a more complex metabolic adaptation. However, this intriguing discovery was partially misinterpreted and disregarded over time. In recent years, the peculiarities of cancer cell metabolism have been re-evaluated in light of new metabolic data that seem to confirm and to widen the original concept of the Warburg effect. In fact, biochemical, molecular, and, above all, proteomic studies on the multifaceted roles of glycolytic enzymes in cancer cells in general, and in cancer stem cells in particular, seem to suggest more complex functional adaptations. These adaptations result in significantly altered protein expression patterns, and they have fundamental implications for diagnosis, prognosis and therapy. Revisiting the Warburg effect in cancer cells with a proteomic approach could deepen our knowledge of cancer cell metabolism and of cancer cell biology in general. Moreover, by identifying useful diagnostic, prognostic and therapeutic targets, it could significantly impact clinical practice.