BIBW 2992 Plus Simvastatin ! [$ d b; i& t3 v @% e, F0 T7 {9 j& p
Detailed Description:
9 W1 o1 `% a- Q( {8 e% gOne of the main reasons of resistance to EGFR tyrosine kinase inhibitors (TKIs) is that there are alternative mechanisms for persistent activating EGFR downstream signaling, including both RAS/Erk and PI3K/Akt kinase pathways. Therefore, simultaneous inhibition of both pathways would be necessary to reduce tumor cell survival more effectively. One of the candidate combinations is concurrent use of EGFR-TKIs and statins, which are irreversible inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase and have been used to treat hypercholesterolemia through blocking the mevalonate biosynthesis pathway. Beside the cholesterol lowering effect, statins have been shown to induce apoptosis in several tumor types. It affects the synthesis of other products of the mevalonate pathway such as isoprenoids, which are used as substrates for prenylation. Attachment of isoprenoids to RAS proteins facilitates their anchoring to the cell membrane where they carried out their roles. By interrupting the biosynthesis of mevalonate, statins inhibit activation of RAS and downstream signaling cascades, including the RAF/MEK/ERK and PI3K/AKT, which play critical roles in regulation of cell survival and proliferation. Therefore, it seems to be a promising therapeutic approach overcoming tumor resistance to EGFR-TKIs, which is associated with RAS activation.
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According to the recent clinical result of phase II trial, a randomized phase II study of gefitinib with or without simvastatin in previously treated patients with advanced NSCLC conducted by Han et al.37 gefitinib plus simvastatin combination produced higher response rates than gefitinib alone in patients with non-adenocarcinoma (5/13 [39%] v 1/13 [8%], P=0.06). This finding suggests that simvastatin may enhance sensitivity to gefitinib in non-adenocarcinoma that is relatively resistant to gefitinib. Moreover, by Mantha et al.35 demonstrated that the combination of gefitinib and lovastatin showed significant synergic cytotoxic effects in vitro in a total of 16 squamous cell carcinomas, NSCLC, and colon carcinoma cell lines. Of special interest, these cell lines did not possess the activating mutations of EGFR, which confer increased sensitivity to gefitinib. Nevertheless, combining lovastatin with gefitinib induced more significant inhibition of AKT activation than either agent alone. Additionally, lovastatin significantly enhanced the sensitivity to gefitinib treatment regardless PTEN loss in glioblastoma cell lines. These results suggest that statins can augment EGFR inhibition., c* ^9 q$ n9 ^& R
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父亲的治疗传来了好消息
父亲今年68岁，从今年三月低确认肺癌晚期到现在，一直没有好消息。胸水基因检测：EGFR
HER2突变肺癌诊疗实现新突破，HER2检
作者：seacat
近几年来靶向和免疫疗法的发展显著改善了肺癌患者的生存期，但仍有一部
安禹堂产品真实反馈
患友使用安禹堂皮肤抑菌液、手足平、甲沟炎凝胶真实反馈
中日友好医院科研转化产品安
肺腺癌egfr21-l858r突变，egfr扩增、
老爸21年3月发现肺腺癌晚期，双肺转移，纵隔淋巴结增大，取组织基因检测结果为egfr21-
【跨越五年】可能是最轻松治疗的肺癌
转载自：Mia和小怪兽
现在刚好距离我爸发现肺癌过去五年了，跟大部分患者比，我爸应
显身卡
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