BIBW 2992 Plus Simvastatin
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One 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.$ \: ?" U" \% N) z1 [% x6 g
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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.+ r D" v, c; `
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肺腺癌晚期ⅣB，基因靶点KARS-G12C，
各位老师，我哥肺腺癌晚期，患有强直性脊柱炎，目前治疗方案为：贝伐单抗＋化疗药，10
发现招募：转移性结直肠癌（mCRC）患
招募：转移性结直肠癌（mCRC）患者
地点：山西医科大学第一医院肿瘤消化科
研究主
肝硬化肝腹水，失代偿，求助哪里医生
家人查出肝硬化肝腹水，年轻时有乙肝，一直状况良好，未治疗，今年由于劳累，感觉没劲
BRCA突变患者迎来高质量长生存，助力
作者：Tony
从2018年第一个PARP抑制剂在我国上市，到如今，想找到一个在临床上还没用
KRAS G12D: 安罗替尼+曲美替尼？
各位朋友请教一下：
基因检测靶点KRAS G12D, 目前单用安罗替尼，但安罗替尼有耐药迹
显身卡
