摘要
化疗是治疗癌症的主要选择。尽管系统的化疗能够有效地根除癌症细胞,显著比例的肿瘤病人表现出化疗抵抗的表型,并导致疾病的恶化、癌症的复发以及存活率的下降。已经明确的是大部分的化疗药物的疗效与他们能够与癌症细胞中特定结构结合后产生的反应活性并促使细胞的死亡有关。由于反复地暴露在化疗药物中,癌症细胞的氧化还原内稳态被持续的破坏,能够使得细胞的能力由处理过度的RS水平变为生产保护性的分子。这个过程所导致地不平衡被称为氧化应激,这是癌症细胞的毒药。自相矛盾的地方是,氧化应激过程中所产生的代谢物却有益于一些癌症亚种的生存,并表现为特定的基因标签,在他们的克隆体上显示出了化疗耐药性的表型。尽管巨大数量的信息通过当前可行技术而产生,我们还不能预测是否这样的抵抗在化疗过程中会发生,而且我们仍然不能全面地了解其发生的机制。在本综述中,我们讨论了关于氧化应激信号传递在癌症化疗中的作用和导致化疗耐药性的核心的氧化还原分子及其通路的主要发现。
关键词: 抗肿瘤药物,癌症,化疗耐药性,化疗,氧化应激,氧化还原内稳态。
Current Medicinal Chemistry
Title:Oxidative Stress, Redox Signaling and Cancer Chemoresistance: Putting Together the Pieces of the Puzzle
Volume: 21 Issue: 28
Author(s): Vanessa Jacob Victorino, Luciana Pizzatti, Pamela Michelletti and Carolina Panis
Affiliation:
关键词: 抗肿瘤药物,癌症,化疗耐药性,化疗,氧化应激,氧化还原内稳态。
摘要: 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.
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Cite this article as:
Jacob Victorino Vanessa, Pizzatti Luciana, Michelletti Pamela and Panis Carolina, Oxidative Stress, Redox Signaling and Cancer Chemoresistance: Putting Together the Pieces of the Puzzle, Current Medicinal Chemistry 2014; 21 (28) . https://dx.doi.org/10.2174/0929867321666140601164647
DOI https://dx.doi.org/10.2174/0929867321666140601164647 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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