Oxidative stress, redox signaling and cancer chemoresistance: putting together the pieces of the puzzle.
Oxidative stress, redox signaling and cancer chemoresistance: putting together the pieces of the puzzle.
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DOI：
10.2174/0929867321666140601164647
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发表时间：
2014-08
影响因子：
4.1
通讯作者：
V. Victorino;L. Pizzatti;Pamela Michelletti;C. Panis
中科院分区：
文献类型：
--
作者：
V. Victorino;L. Pizzatti;Pamela Michelletti;C. Panis
化疗仍然是癌症的主要治疗选择。虽然全身化疗可以有效地根除癌细胞，但相当一部分患者携带的肿瘤呈现出化疗耐药表型，导致疾病进展、癌症复发和生存率降低。也已经清楚的是，大多数化疗药物的效果与它们产生反应性物质（RS）的能力有关，所述反应性物质（RS）结合到癌细胞内的特定结构并促进细胞死亡。由于反复暴露于化疗剂，癌细胞的氧化还原稳态不断受到干扰，这可能导致细胞通过产生保护性分子科普过量RS水平的能力发生变化。据认为，这一过程导致的不平衡-氧化应激-对癌细胞是有毒的。有趣的是，在氧化应激过程中产生的代谢物可以有利于一些癌症亚群的生存，这些亚群呈现特定的基因特征，赋予这些克隆化学抗性表型。尽管目前可用的技术产生了大量的信息，但我们无法预测这种耐药性是否会在化疗期间出现，我们仍然不完全了解其产生的机制。在这篇综述中，我们讨论了氧化应激信号在癌症化疗中的作用以及导致化疗耐药性发展的关键氧化还原分子和途径的主要发现。
Chemotherapy continues to be the main treatment option for cancer. Although systemic chemotherapy can efficiently eradicate cancer cells, a significant proportion of patients carry tumors that present a chemoresistant phenotype, resulting in disease progression, cancer relapse, and reduced survival. It has also become clear that the effect of most chemotherapeutic drugs is associated with their capacity to generate reactive species (RS) that bind to specific structures within the cancer cell and promote cell death. Due to repeated exposure to chemotherapeutic agents, the redox homeostasis of cancer cells is continuously disturbed, which can result in changes to the cell's ability to cope with excessive RS levels through the production of protective molecules. It is thought that the imbalance resulting from this process-- oxidative stress--is toxic to cancer cells. Paradoxically, the metabolites produced during oxidative stress can favor the survival of some cancer subpopulations, which present specific gene signatures that confer a chemoresistant phenotype on these clones. Despite the huge amount of information generated by currently available technologies, we cannot predict whether this resistance will arise during chemotherapy and we still do not fully understand the mechanism by which it arises. In this review, we discuss the main findings regarding the role of oxidative stress signaling in cancer chemotherapy and the key redox molecules and pathways that lead to the development of chemoresistance.