Profiles of Radioresistance Mechanisms in Prostate Cancer.
Profiles of Radioresistance Mechanisms in Prostate Cancer.
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DOI：
10.1615/critrevoncog.2018025946
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发表时间：
2018
影响因子：
--
通讯作者：
Kyprianou N
中科院分区：
文献类型：
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作者：
Chaiswing L;Weiss HL;Jayswal RD;Clair DKS;Kyprianou N
放射疗法（RT）通常用于治疗局限性前列腺癌（PCa）。然而，癌细胞通常通过未知的机制对辐射产生抗性，并构成棘手的挑战。放射抵抗是高度不可预测的，使得治疗在许多患者中效果不佳，并且经常导致转移和癌症复发。了解导致PCa放射抗性的分子事件将使我们能够开发用于增强RT功效的辅助治疗。放射抗性PCa依赖于升高的DNA修复系统和细胞内活性氧（ROS）水平来增殖、自我更新和抑制抗癌方案，而升高的热休克蛋白90（HSP 90）和上皮-间充质转化（EMT）使抗辐射PCa细胞在暴露于辐射后发生转移。DNA修复系统、ROS、HSP 90和EMT效应子的上调已被广泛研究，但未被放射抗性PCa的辅助治疗靶向。在这里，我们强调电离辐射的影响和机制驱动的耐辐射PCa的出现。我们还讨论了放射抗性的标志物，对放射治疗的预测反应的基因特征，以及针对放射抗性PCa的新型治疗平台。这篇综述提供了重要的见解，以提高目前的知识和理解对这些标记物的治疗放射抵抗性前列腺癌的优化。
Radiation therapy (RT) is commonly used for the treatment of localized prostate cancer (PCa). However, cancer cells often develop resistance to radiation through unknown mechanisms and pose an intractable challenge. Radiation resistance is highly unpredictable, rendering the treatment less effective in many patients and frequently causing metastasis and cancer recurrence. Understanding the molecular events that cause radioresistance in PCa will enable us to develop adjuvant treatments for enhancing the efficacy of RT. Radioresistant PCa depends on the elevated DNA repair system and the intracellular levels of reactive oxygen species (ROS) to proliferate, self-renew, and scavenge anti-cancer regimens, whereas the elevated heat shock protein 90 (HSP90) and the epithelial-mesenchymal transition (EMT) enable radioresistant PCa cells to metastasize after exposure to radiation. The up-regulation of the DNA repairing system, ROS, HSP90, and EMT effectors has been studied extensively, but not targeted by adjuvant therapy of radioresistant PCa. Here, we emphasize the effects of ionizing radiation and the mechanisms driving the emergence of radioresistant PCa. We also address the markers of radioresistance, the gene signatures for the predictive response to radiotherapy, and novel therapeutic platforms for targeting radioresistant PCa. This review provides significant insights into enhancing the current knowledge and the understanding toward optimization of these markers for the treatment of radioresistant PCa.