Chiu Martina, Ottaviani Laura, Bianchi Massimiliano G, Franchi-Gazzola Renata, Bussolati Ovidio
Unit of General Pathology, Department of Biomedical, Biotechnological and Translational Sciences, University of Parma, Italy.
Acta Biomed. 2012 Dec;83(3):168-76.
It is increasingly appreciated that cancer cells must be endowed with specific metabolic adaptations to support enhanced growth and to ensure survival under stressful conditions. On the other hand, many oncogenic mutations of protooncogenes and tumor suppressor genes directly cause metabolic derangements and, conversely, mutations of enzymes have been found to underlie several forms of cancer. Thus, cancer-specific metabolic alterations are now considered among the hallmarks of malignant tumors. Most commonly, cancer cells exhibit enhanced glycolysis under aerobic conditions (the Warburg effect) but alterations in the metabolism of amino acids, such as glutamine, serine and proline are increasingly described as important metabolic features of selected tumor types. In theory, all these deranged cancer-specific metabolic pathways may constitute novel therapeutic targets, although the only "metabolic" drug in clinical use is still represented by the enzyme L-asparaginase. However, the increasing amount of experimental evidence, as well as the number of trials in progress, suggests that metabolic drugs will soon complement standard anti-cancer chemotherapy and modern biological drugs.
人们越来越认识到，癌细胞必须具备特定的代谢适应性，以支持其增强的生长并确保在应激条件下存活。另一方面，许多原癌基因和肿瘤抑制基因的致癌突变直接导致代谢紊乱，反之，已发现酶的突变是几种癌症形式的基础。因此，癌症特异性代谢改变现在被认为是恶性肿瘤的标志之一。最常见的是，癌细胞在有氧条件下表现出增强的糖酵解（瓦伯格效应），但氨基酸代谢的改变，如谷氨酰胺、丝氨酸和脯氨酸，越来越多地被描述为特定肿瘤类型的重要代谢特征。理论上，所有这些紊乱的癌症特异性代谢途径都可能构成新的治疗靶点，尽管临床上唯一使用的“代谢”药物仍然是L-天冬酰胺酶。然而，越来越多的实验证据以及正在进行的试验数量表明，代谢药物很快将补充标准抗癌化疗和现代生物药物。
