《自然》双重磅：击中癌症转移软肋！专家首次发掘，Netrin-1掌控剂可掌控肿瘤的上皮间质转化，或能预防癌症转移，破解化疗耐药
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">*仅供医学专业人士阅读参考</span></p>
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<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">Netrin-1是一种在多癌种中表达上调的蛋白，<span style="color: black;">已然</span>有临床<span style="color: black;">科研</span>在晚期实体瘤<span style="color: black;">病人</span>中测试了Netrin-1中和抗体NP137的实力。</span></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">今日，《自然》杂志在线<span style="color: black;">发布</span>两篇<span style="color: black;">关联</span>论文，法国和比利时的<span style="color: black;">研究</span>团队联手分析了该<span style="color: black;">科研</span>中子宫内膜癌<span style="color: black;">病人</span>数据，并对NP137<span style="color: black;">功效</span>机制进行了分析。<span style="color: black;">科研</span>者<span style="color: black;">发掘</span>，<span style="color: black;"><strong style="color: blue;">阻断Netrin-1<span style="color: black;">功效</span>在诱导肿瘤细胞死亡之外，还可<span style="color: black;">控制</span>上皮-间充质转化（EMT），或有助于减轻对标准治疗的耐药性</strong></span>。</span></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><strong style="color: blue;"><span style="color: black;">临床<span style="color: black;">科研</span>中，14位晚期子宫内膜癌<span style="color: black;">病人</span>中有8例实现<span style="color: black;">疾患</span>稳定（SD）、1例部分缓解（PR）</span></strong><span style="color: black;">。</span></p><img src="https://mmbiz.qpic.cn/sz_mmbiz_png/g1rJAV614wyW0Q2SaKKyV6daKyGyOMIrPER42bOl2MxeRd7toeqJr8zR7X9UAeaasoPKTHPfkjKo6Zibr14I14w/640?wx_fmt=png&tp=webp&wxfrom=5&wx_lazy=1&wx_co=1" style="width: 50%; margin-bottom: 20px;"><img src="https://mmbiz.qpic.cn/sz_mmbiz_png/g1rJAV614wyW0Q2SaKKyV6daKyGyOMIryic8o6CRU8No7pRUj9hYx0PxuafH9CPnCEaK0ibpz73Nh9ia3ydhrCp6A/640?wx_fmt=png&tp=webp&wxfrom=5&wx_lazy=1&wx_co=1" style="width: 50%; margin-bottom: 20px;">
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">论文题图</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">Netrin-1是一种胚胎分泌的层黏连蛋白<span style="color: black;">关联</span>糖蛋白，它在神经元导航、血管生成和细胞存活中<span style="color: black;">相关</span>键<span style="color: black;">功效</span>。Netrin-1<span style="color: black;">重点</span>在胚胎<span style="color: black;">生长</span>过程中表达，在诸如炎症<span style="color: black;">关联</span>的结直肠癌、乳腺癌肺转移癌、神经母细胞瘤、淋巴瘤、黑色素瘤等人类肿瘤中<span style="color: black;">亦</span>有表达。</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">在临床前<span style="color: black;">科研</span>中，有<span style="color: black;">科研</span>者<span style="color: black;">发掘</span>，阻断Netrin-1与其受体相互<span style="color: black;">功效</span><span style="color: black;">能够</span>触发癌细胞死亡并<span style="color: black;">控制</span>肿瘤生长。</span></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">Netrin-1的中和抗体NP137能够阻断Netrin-1与受体UNC5B的相互<span style="color: black;">功效</span>。在1期临床<span style="color: black;">科研</span>（NCT02977195）中，初步<span style="color: black;">评定</span>了NP137对晚期实体瘤的安全性和有效性，其中就<span style="color: black;">包含</span>子宫内膜癌（EC）。</span></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;"><span style="color: black;">科研</span>中<span style="color: black;">包含</span>14名晚期子宫内膜癌<span style="color: black;">病人</span>，NP137每双周给药，直到临床<span style="color: black;">发展</span>。<strong style="color: blue;">8名<span style="color: black;">病人</span>（57.1%）实现<span style="color: black;">疾患</span>稳定，1名<span style="color: black;">病人</span>实现RECIST1.1定义的部分缓解，6周病变减少51.16%、6个月病变减少54.65%</strong>
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<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">病人</span>反应</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">为了搞清楚Netrin-1与肿瘤生长之间的关系，<span style="color: black;">科研</span>者在Ptenf/f小鼠中进行了实验，这种小鼠可快速发展出原位子宫内膜癌。</span></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">可见NP137<span style="color: black;">增多</span>癌细胞凋亡；RNA测序<span style="color: black;">表示</span>，NP137治疗后EpCAM上皮标志物<span style="color: black;">明显</span><span style="color: black;">增多</span>，间充质基因表达减少、上皮基因表达<span style="color: black;">增多</span>，EMT评分<span style="color: black;">明显</span>降低。</span></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">以上结果说明，<strong style="color: blue;">Netrin-1<span style="color: black;">控制</span>对肿瘤细胞的<span style="color: black;">功效</span>是双重的，一方面触发癌细胞死亡，另一方面<span style="color: black;">控制</span>EMT</strong>。</span></p><img src="https://mmbiz.qpic.cn/sz_mmbiz_png/g1rJAV614wyW0Q2SaKKyV6daKyGyOMIr5fQJHeLKdArqIqX5QpLeVicPiaR3fv4TEoRG3cAsgGJE3YAJZBgjTNiag/640?wx_fmt=png&tp=webp&wxfrom=5&wx_lazy=1&wx_co=1" style="width: 50%; margin-bottom: 20px;">
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">NP137治疗<span style="color: black;">增多</span>肿瘤细胞凋亡（上），<span style="color: black;">控制</span>EMT（下）</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">在接受治疗的<span style="color: black;">病人</span>中，<span style="color: black;">一样</span>观察到了EMT评分的<span style="color: black;">明显</span>降低和上皮表型的转化。</span></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">单细胞水平分析<span style="color: black;">表示</span>，NP137大幅度减少了肿瘤细胞比例，<span style="color: black;">况且</span>对免疫细胞<span style="color: black;">一样</span>存在影响，CD8阳性</span><span style="color: black;">T细胞和NK细胞数量<span style="color: black;">增多</span>。</span><span style="color: black;">空间转录组数据<span style="color: black;">表示</span>，T细胞和肿瘤细胞之间的相互<span style="color: black;">功效</span>数量和强度都有所<span style="color: black;">增多</span>，M2巨噬细胞减少，MHCI/II类抗原递呈<span style="color: black;">增多</span>。</span></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">有<span style="color: black;">海量</span><span style="color: black;">科研</span>指出，EMT是化疗耐药的<span style="color: black;">重点</span><span style="color: black;">原由</span>。<span style="color: black;">因此呢</span><span style="color: black;">科研</span>者在小鼠中测试了NP137与卡铂-紫杉醇联用的效果，这是治疗子宫内膜癌的标准治疗<span style="color: black;">方法</span>。实验结果<span style="color: black;">表示</span>，二者联用效果优于单独<span style="color: black;">运用</span>卡铂-紫杉醇，说明Netrin-1<span style="color: black;">控制</span>剂或许<span style="color: black;">能够</span>用于减轻对常规疗法的耐药。</span></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">另一</span>一项<span style="color: black;">科研</span>则在皮肤鳞状细胞癌小鼠中进行，<span style="color: black;">一样</span>证实了靶向Netrin-1可<span style="color: black;">控制</span>EMT。</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">这是首次<span style="color: black;">知道</span>证实Netrin-1对EMT的调节<span style="color: black;">功效</span>。EMT在肿瘤的<span style="color: black;">出现</span>、<span style="color: black;">发展</span>、转移、耐药等多个<span style="color: black;">周期</span>皆存在<span style="color: black;">功效</span>，<span style="color: black;">然则</span><span style="color: black;">日前</span>仍然<span style="color: black;">无</span><span style="color: black;">药品</span>能够实质性<span style="color: black;">干涉</span>EMT特征。或许，NP137将<span style="color: black;">作为</span>破局的关键一子。</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">正在进行的2期临床<span style="color: black;">科研</span>GYNET（NCT04652076）中对NP137与卡铂-紫杉醇和帕博利珠单抗的联合<span style="color: black;">运用</span>进行了探索，<span style="color: black;">咱们</span><span style="color: black;">能够</span>期待一下它即将交出的答案。</span></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;"><strong style="color: blue;"><span style="color: black;"><img src="https://mmbiz.qpic.cn/sz_mmbiz_png/kX6icibYb0ibLopzXEkBLYt6tlqfoib7kkv6XHNpkq8ZYmHuKLZicRZ1v9fibaibiaE1r3rNVCOibkr2BFN7Q1uhT0PGIgg/640?wx_fmt=png&wxfrom=5&wx_lazy=1&wx_co=1&tp=webp" style="width: 50%; margin-bottom: 20px;"></span></strong></span></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">参考资料：</span></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">Cassier, P.A., Navaridas, R., Bellina, M. et al. Netrin-1 blockade inhibits tumour growth and EMT features in endometrial cancer. Nature (2023).</span><span style="color: black;">https://doi.org/10.1038/s41586-023-06367-z</span></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">Lengrand, J., Pastushenko, I., Vanuytven, S. et al. Pharmaco</span><span style="color: black;">logical targeting of netrin-1 inhibits EMT in cancer. Nature (2023). https://doi.org/10.1038/s41586-023-06372-2</span></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><img src="https://mmbiz.qpic.cn/mmbiz_gif/g1rJAV614wxF0gVj00QktSlORObe2rjyIP0q9r5FXV57GZkn8Tyo2Z5icOjfbNVcsbugu1ia2jQVpQ4aKuadlO4g/640?wx_fmt=gif&wxfrom=5&wx_lazy=1&tp=webp" style="width: 50%; margin-bottom: 20px;"></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;"><img src="https://mmbiz.qpic.cn/mmbiz_png/g1rJAV614wzpwBE0hu5vwicIQ9fPp6QLUbCKDm8Gick8MF4f05XzjeZKjVWJJVYKckw7ODPXg2jibxp3IPgA14Kmw/640?wx_fmt=jpeg&wxfrom=5&wx_lazy=1&wx_co=1&tp=webp" style="width: 50%; margin-bottom: 20px;"></span></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">本文作者丨代丝雨</span></p>
说得好啊！我在外链论坛打滚这么多年，所谓阅人无数，就算没有见过猪走路，也总明白猪肉是啥味道的。
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