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Receptor signaling as a regulatory mechanism of DNA repair.

机译:受体信号传导是DNA修复的调节机制。

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摘要

Radiotherapy plays a crucial role in the treatment of many malignancies; however, locoregional disease progression remains a critical problem. This has stimulated laboratory research into understanding the basis for tumor cell resistance to radiation and the development of strategies for overcoming such resistance. We know that some cell signaling pathways that respond to normal growth factors are abnormally activated in human cancer and that these pathways also invoke cell survival mechanisms that lead to resistance to radiation. For example, abnormal activation of the epidermal growth factor receptor (EGFR) promotes unregulated growth and is believed to contribute to clinical radiation resistance. Molecular blockade of EGFR signaling is an attractive strategy for enhancing the cytotoxic effects of radiotherapy and, as shown in numerous reports, the radiosensitizing effects of EGFR antagonists correlate with a suppression of the ability of the cells to repair radiation-induced DNA double strand breaks (DSBs). The molecular connection between the EGFR and its governance of DNA repair capacity appears to be mediated by one or more signaling pathways downstream of this receptor. The purpose of this review is to highlight what is currently known regarding EGFR signaling and the processes responsible for repairing radiation-induced DNA lesions that would explain the radiosensitizing effects of EGFR antagonists.
机译:放射疗法在许多恶性肿瘤的治疗中起着至关重要的作用。然而,局部疾病的进展仍然是一个关键问题。这刺激了实验室研究,以了解肿瘤细胞对辐射的抗性基础以及克服这种抗性的策略的发展。我们知道某些对正常生长因子有反应的细胞信号通路在人类癌症中被异常激活,并且这些通路还激活了导致对辐射产生抗性的细胞存活机制。例如,表皮生长因子受体(EGFR)的异常激活促进了不受调节的生长,并被认为有助于临床的抗辐射性。 EGFR信号传导的分子阻断是增强放射治疗细胞毒性作用的一种有吸引力的策略,并且,如许多报道所表明的那样,EGFR拮抗剂的放射增敏作用与细胞修复辐射诱导的DNA双链断裂的能力受到抑制有关( DSB)。表皮生长因子受体及其对DNA修复能力的控制之间的分子联系似乎是由该受体下游的一个或多个信号通路介导的。这篇综述的目的是强调有关EGFR信号传导的当前已知信息以及负责修复辐射诱导的DNA损伤的过程,这些过程可以解释EGFR拮抗剂的放射致敏作用。

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