Alteration of cellular metabolism in cancer cells and its therapeutic prospects

Abstract

Transformation of a normal cell into a cancerous phenotype is essentially backed by genetic mutations that trigger several oncogenic signaling pathways. These signaling pathways rewire the cellular metabolism to meet the bioenergetic and biomass requirement of proliferating cell, which is different from a quiescent cell. Although the change of metabolism in a cancer cell was observed and studied in the mid-20^th century, it was not adequate to explain oncogenesis. Now, equipped with a revolution of oncogenes, we have a genetic basis to explain the transformation. Through several studies, it is clear now that such metabolic alterations not only promote cancer progression but also contribute to the chemoresistance of cancer. Targeting specific enzymes and combinations of enzymes can improve the efficacy of cancer therapy and help to overcome the therapeutic resistance.

Keywords: Cancer cell; metabolic alterations; therapeutics.

Figure 1

Glucose metabolism (represented by solid lines) in a quiescent cell

Figure 2

Genetic mutations of gene such as RAS and PTEN can trigger several oncogenic signaling pathways such as PI3K and mammalian target of rapamycin that in turn upregulate glucose transporters and enzymes that catalyze various steps of glycolysis, thus favoring aerobic glycolysis

Figure 3

Reprogramming of metabolism in cancer cells, deprived of glucose and glutamine (reduced intake represented by dotted lines). Pool of amino acids and tricarboxylic acid cycle intermediates, required are maintained by activating pathways that promote autophagy, macropinocytosis and scavenging fatty acids