Metabolic Features of Cancer Treatment Resistance
Metabolic Features of Cancer Treatment Resistance
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DOI：
10.1007/978-3-319-42118-6_6
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发表时间：
2016-01-01
期刊：
影响因子：
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通讯作者：
Draetta, Giulio F.
中科院分区：
文献类型：
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作者：
Viale, Andrea;Draetta, Giulio F.
在肿瘤患者中实现持久缓解和最终治愈的主要障碍是肿瘤耐药性的出现，这是不同疾病类型的常见结果，并且与所采取的治疗方法无关。近年来，在不同的肿瘤中分离出了具有增强的致瘤潜力和多药耐药的慢循环细胞亚群，越来越多的实验证据表明这些耐药细胞是肿瘤复发的原因。对耐药肿瘤干细胞的深入代谢表征表明，它们比其他肿瘤细胞更依赖于线粒体呼吸，而较少依赖于糖酵解，这一发现挑战了肿瘤主要具有糖酵解代谢和线粒体缺陷的假设。在大多数肿瘤中可能存在的耐药致瘤细胞中的代谢程序的证明具有重要的治疗意义，并且是我们解决识别可能在治疗上利用的新漏洞的挑战时的关键考虑因素。
A major barrier to achieving durable remission and a definitive cure in oncology patients is the emergence of tumor resistance, a common outcome of different disease types, and independent from the therapeutic approach undertaken. In recent years, subpopulations of slow-cycling cells endowed with enhanced tumorigenic potential and multidrug resistance have been isolated in different tumors, and mounting experimental evidence suggests these resistant cells are responsible for tumor relapse. An in-depth metabolic characterization of resistant tumor stem cells revealed that they rely more on mitochondrial respiration and less on glycolysis than other tumor cells, a finding that challenges the assumption that tumors have a primarily glycolytic metabolism and defective mitochondria. The demonstration of a metabolic program in resistant tumorigenic cells that may be present in the majority of tumors has important therapeutic implications and is a critical consideration as we address the challenge of identifying new vulnerabilities that might be exploited therapeutically.