Children's Research Institute and Department of Pediatrics, The University of Texas Southwestern Medical Center, Dallas, Texas.
Howard Hughes Medical Institute, The University of Texas Southwestern Medical Center, Dallas, Texas.
Cancer Discov. 2021 Nov;11(11):2682-2692. doi: 10.1158/2159-8290.CD-21-0558. Epub 2021 Oct 14.
Metastasis is an inefficient process in which the vast majority of cancer cells are fated to die, partly because they experience oxidative stress. Metastasizing cancer cells migrate through diverse environments that differ dramatically from their tumor of origin, leading to redox imbalances. The rare metastasizing cells that survive undergo reversible metabolic changes that confer oxidative stress resistance. We review the changes in redox regulation that cancer cells undergo during metastasis. By better understanding these mechanisms, it may be possible to develop pro-oxidant therapies that block disease progression by exacerbating oxidative stress in cancer cells. SIGNIFICANCE: Oxidative stress often limits cancer cell survival during metastasis, raising the possibility of inhibiting cancer progression with pro-oxidant therapies. This is the opposite strategy of treating patients with antioxidants, an approach that worsened outcomes in large clinical trials.
转移是一个效率低下的过程，在此过程中，绝大多数癌细胞注定会死亡，部分原因是它们经历了氧化应激。转移性癌细胞通过与起源肿瘤截然不同的各种环境迁移，导致氧化还原失衡。少数能够存活的转移性细胞会经历可逆的代谢变化，从而获得对氧化应激的抗性。我们回顾了癌细胞在转移过程中经历的氧化还原调控变化。通过更好地了解这些机制，有可能开发出促氧化剂疗法，通过在癌细胞中加剧氧化应激来阻止疾病进展。意义：氧化应激通常会限制癌细胞在转移过程中的存活，从而有可能通过促氧化剂疗法来抑制癌症进展。这与用抗氧化剂治疗患者的策略相反，在大型临床试验中，这种方法使结果恶化。
