The RAS signal transduction pathway and its role in radiation sensitivity
The RAS signal transduction pathway and its role in radiation sensitivity
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DOI：
10.1038/sj.onc.1206699
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发表时间：
2003-09-01
期刊：
影响因子：
8
通讯作者：
Bernhard, EJ
中科院分区：
文献类型：
--
作者：
McKenna, WG;Muschel, RJ;Bernhard, EJ
RAS已被证明可以增加辐射抗性。因此，RAS的上游和下游途径可能是操纵放射敏感性的靶点。EGFR表达和AKT磷酸化也与对辐射的反应相关。一项回顾性研究在接受多模式治疗的患者中评估了EGFR和AKT，发现P-AKT与治疗失败之间存在显著相关性。此外，这些数据通过显示EGFR、RAS、PI 3 K和AKT放射致敏癌细胞系的抑制的体外研究得到加强。我们以前已经表明，PI 3 K是RAS诱导的辐射抗性的介质。我们现在认为，EGFR，这是上游的PI 3 K，也可能通过一个共同的途径介导的阻力。除了EGFR和RAS，PTEN还可以调节PI 3 K通路。识别导致辐射抗性的EGFR、RAS或PTEN的共同信号可能会发现开发基于分子的放射增敏方案的靶点，从而改善局部控制。
RAS has been shown to increase radiation resistance. Upstream and downstream pathways from RAS could thus be targets for manipulation of radiosensitivity. EGFR expression and AKT phosphorylation are also associated with the response to radiation. A retrospective study evaluating EGFR and AKT in patients treated with multimodality therapy found a significant association between P-AKT and treatment failure. Moreover, these data are strengthened by in vitro studies showing that inhibition of EGFR, RAS, PI3K, and AKT radiosensitized cancer cell lines. We have previously shown that PI3K is a mediator of RAS-induced radiation resistance. We now suggest that EGFR, which is upstream of PI3K, may also mediate resistance through a common pathway. In addition to EGFR and RAS, PTEN can also regulate the PI3K pathway. Identifying a common signal for EGFR, RAS, or PTEN that results in radiation resistance may uncover targets for developing molecular-based radiosensitization protocols for tumors resistant to radiation and thus improve local control.