Effect of nintedanib, a triple angiokinase inhibitor, on EGFR and HER2 in colorectal cancer (CRC) models, and rational for its combinations with the ErbB family blocker afatinib.
http://meetinglibrary.asco.org/content/123071-143
Abstract:
Background: We have recently shown that combinations of afatinib, a pan-HER/ErbB blocker, and nintedanib, a triple angiokinase (VEGFR, FGFR, PDGFR) inhibitor show synergistic activity in CRC models (Poindessous et al., Clin Cancer Res. 17:6522, 2011). However, the mechanistic basis for the synergistic effects of the combination is incompletely understood. EGFR is activated following exposure to a wide variety of therapeutic modalities including ionizing irradiation and irinotecan. We speculated that nintedanib exposure could also activate EGFR signaling which might explain the synergistic activity of the combination. Methods: Mice with human CRC xenografts were treated with nintedanib and afatinib alone or in combination and the influence on tumor growth, viability and the presence of phosphorylated HER family members was determined. Different scheduling regimens were explored to identify an administration schedule which combined optimal antitumor activity with minimal toxic side effects. Results: We here show that nintedanib treatment results in activation of EGFR and HER2 in multiple CRC xenograft models in a dose-dependent manner. Among the different regimens tested, continuous nintedanib with administration of afatinib every second week proved almost as efficient as continuous administration of the two agents together and was less toxic. Finally, nintedanib plus afatinib was superior to nintedanib alone in three different tumor xenografts with mutant KRAS. Conclusions: We here report that prolonged exposure to nintedanib, a small molecule angiogenesis inhibitor, is accompanied by activation of EGFR and HER2. Accordingly, afatinib, an ErbB family blocker, was synergistic with nintedanib. We subsequently identified a novel regimen for optimizing the antitumor effects of the combination with limited toxic side effects and showed that this regimen is active in four different CRC tumor models including three with mutant KRAS. These findings provide a rationale for clinical trials of the two small molecules, even in patients with mutant KRAS.
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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
