Overexpression of wild type KRAS increased the IC50 (inhibitory concentration of drug that decreases cell viability to 50%) to crizotinib from 0.16 μM to 1.68 μM (p-value < 0.001) (Figure 4A, ,4G)4G) and NF1 downregulation increased the IC50 to crizotinib from 0.16 μM to 0.75 μM (p-value < 0.001) (Figure 4D, ,4H).4H). Treatment of cells harboring both METex14 and KRAS overexpression with the combination of crizotinib and the MEK inhibitor trametinib in order to block both MET signaling and downstream MAPK pathway signaling restored sensitivity to treatment (crizotinib IC50 of 1.68 μM in the absence of trametinib versus 0.25 μM with trametinib co-treatment, p-value < 0.001) (Figure 4B, ,4G).4G). Similarly, co-treatment of cells harboring both METex14 and NF1 downregulation with both trametinib and crizotinib restored sensitivity to treatment (crizotinib monotherapy IC50 0.75 μM versus 0.18 μM upon addition of trametinib, p-value < 0.001 (Figure 4E, ,4H).4H). The selected trametinib dose modestly reduced but did not eliminate cell growth in the absence of crizotinib (Supplemental Figure S5). Immunoblotting demonstrated sustained Erk phosphorylation despite crizotinib treatment in samples with KRAS overexpression or NF1 downregulation, which was abrogated by the addition of trametinib (Figure 4C, ,4F).4F). In both genomic contexts, combination treatment was associated with increased levels of cleaved PARP, indicative of apoptosis, which was absent with monotherapy (Figure 4C, ,4F4F).
建设性意见 |
都说免疫不入脑，入了就不得了
免疫治疗以后的疗效反应，当病灶增大时，不一定是进展，还有一种可能，叫做CR，这个现
母亲的基因检测和PD-L1报告出来了，
看了基因检测报告，似乎没有合适的靶向药，母亲确诊肺腺癌晚期，求助大家帮忙分析一下
头部长个包 免疫性副反应吗
我们已经治疗将近四年了 一直用的单免疫治疗 没有用其他治疗 之前用的信迪利 今年初
晚期肺癌经过4次换药，如今母亲已经4
作者：pears
“万事开头难”这句话在母亲的抗癌路上体现得淋漓尽致，最初确诊肺癌后半
既要，又要，还要，什么药品可以治疗
作者：seacat
EGFR突变可以分为常见突变和罕见突变。常见突变就是EGFR外显子19del突变
显身卡
