是由两位生物医药领域的科研工作者发起的聊天类播客。我们关注生命如何走到今天，以及如何让ta更好。
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ATGC doctors' chat
Claim This Podcastby 雅娴，莲燕，王祎
5.0(2 reviews)
65 episodes
Updated Bi-weekly
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Podcast Overview
是由两位生物医药领域的科研工作者发起的聊天类播客。我们关注生命如何走到今天，以及如何让ta更好。 商务合作：zyx3200@163.com
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Publishing Since
6/10/2022
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Recent Episodes
June 7, 2026
从「不可成药」到改写胰腺癌生存曲线：一个分子开关的 40 年战争
<p></p><p>2026 年 5 月底，一项名为 RESolute 302 的三期临床试验结果登上了 ASCO 压轴场。10 多年来，胰腺癌的中位总生存期，都卡在 6 个月出头，而一款叫做 Daraxonrasib 的新药，把这个数字拉到了 13.2 个月——死亡风险下降了 60%。</p><p>为什么这件事如此震撼？因为它攻克的靶点叫做 KRAS——一个 1982 年就已被发现、与三成人类癌症相关、在胰腺癌中突变率接近 95%，却被整个科学界宣判了近 40 年"不可成药"的基因。这期节目里，我们聊了聊 RAS 蛋白到底是什么，它为什么那么难成药；第一代 KRAS 药物是为什么对胰腺癌几乎无效；以及 Daraxonrasib 是怎样突破“不可成药”的极限的。</p><p><strong>时间轴</strong></p><p>[<a class="timestamp">00:13</a>] Daraxonrasib 将胰腺癌的中位生存期延长了一倍</p><p>[<a class="timestamp">02:30</a>] RAS 靶点：癌症研究的珠穆朗玛峰</p><p>[<a class="timestamp">03:59</a>] RAS 基因突变如何让细胞失控增殖？</p><p>[<a class="timestamp">10:42</a>] RAS 为什么难成药？</p><p>[<a class="timestamp">12:53</a>] 第一代 KRAS 抑制剂：历史性突破，也有明显边界</p><p>[<a class="timestamp">15:30</a>] Daraxonrasib 的 tri-complex 药物设计框架</p><p>[<a class="timestamp">19:25</a>] RESolute 302：突破性的临床试验结果</p><p>[<a class="timestamp">22:52</a>] 耐药性：靶向药的难题</p><p></p><p>Tri-complex 药物设计框架</p><img src="https://image.xyzcdn.net/FvKAgBUJDfszuJj3hLHkwQxczrw3.png"><p><br></p><p><strong>参考文献</strong></p><p><strong>[1] RASolute 302 三期临床试验（NEJM，主论文）</strong> O'Reilly EM, Wainberg ZA, Hendifar AE, et al. Daraxonrasib or chemotherapy in previously treated metastatic pancreatic cancer. N Engl J Med. 2026 May 31. doi: 10.1056/NEJMoa2605555</p><p><strong>[2] RMC-6236-001 一/二期临床试验（NEJM，奠基数据）</strong> Wolpin BM, Park W, Garrido-Laguna I, et al. Daraxonrasib in previously treated advanced RAS-mutated pancreatic cancer. N Engl J Med. 2026;394(18):1790–1802. doi: 10.1056/NEJMoa2505783</p><p><strong>[3] Switch II Pocket 发现论文（Shokat 实验室，Nature，2013）</strong> Ostrem JM, Peters U, Sos ML, Wells JA, Shokat KM. K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions. Nature. 2013;503(7477):548–551. doi: 10.1038/nature12796</p><p><strong>[4] Sotorasib 关键临床论文（CodeBreaK 100，NEJM，2021）</strong> Skoulidis F, Li BT, Dy GK, et al. Sotorasib for lung cancers with KRAS p.G12C mutation. N Engl J Med. 2021;384(25):2371–2381. doi: 10.1056/NEJMoa2103695</p><p><strong>[7] RASolute 302 Plenary Session 报告</strong> Wolpin BM. Daraxonrasib, a RAS(ON) multi-selective inhibitor vs chemotherapy in previously treated metastatic pancreatic adenocarcinoma (mPDAC): primary and final analysis from the phase 3 RASolute 302 study. Presented at: 2026 ASCO Annual Meeting; May 31, 2026; Chicago, IL. Abstract LBA5.</p><p><br></p><p><strong>📬【联系我们】</strong></p><p>联系我们：zyx3200@163.com</p><p>微信：atgcdoctorschat，备注「加听友群」</p><p></p><br><a href="https://oia.xiaoyuzhoufm.com/player/6a2585dea3b280185f5d6f55?openTranscript=true&utm_source=rss&as=cHQ9MTIyNjE5MjQ3JmN0PXJzcyZtdD04&autoOpen=false">在小宇宙查看该单集文稿</a>
June 2, 2026
抗抑郁药研发史：被误解的「血清素」
<p>SSRI，全称 selective serotonin reuptake inhibitor，中文叫做选择性血清素再摄取抑制剂，是目前全球使用最广泛的抗抑郁药物。百忧解、左洛复、来士普，这些名字你可能不陌生。仅在美国，2023年就有约11.4%的成年人在服用抗抑郁药物处方。在全球抗抑郁药市场中，SSRI 占据了超过55%的份额，市场规模在2024年达到187亿美元，而且还在持续增长。</p><p>这类药物之所以能走到今天的位置，背后有一个支撑它的理论——「血清素假说」，也就是抑郁症是因为大脑里的血清素不足。这个假说塑造了几十年来医生开药的逻辑，也塑造了无数患者对自己疾病的理解方式。但问题在于，这个理论从来没有在人体上被直接证明过。</p><p>这期节目我们聊一聊，血清素假说从何而来，又有哪些证据动摇了它；如果血清素不是答案，科学界目前的新方向是什么；以及两类颠覆性的新药为什么值得关注。</p><p><strong>时间轴</strong></p><p>[<a class="timestamp">01:48</a>] 我们为什么会抑郁？「血清素假说」的起点</p><p>[<a class="timestamp">04:32</a>] 早期抗抑郁药的困境：靶点太多，副作用太大</p><p>[<a class="timestamp">06:03</a>] 「 百忧解」的诞生：寻找"干净分子"</p><p>[<a class="timestamp">09:52</a>] 「血清素假说」的逻辑漏洞：药能治病≠身体缺这种</p><p>[<a class="timestamp">15:29</a>] SSRIs 为什么有效？从单一分子到网络和系统</p><p>[<a class="timestamp">18:37</a>] 艾司氯胺酮和裸盖菇素：绕开血清素的两条路</p><p>[<a class="timestamp">20:52</a>] 血清素假说不是错的，只是太简单</p><p><strong>参考文献</strong></p><ol><li><p>Schildkraut, J. J. (1965). The catecholamine hypothesis of affective disorders: a review of supporting evidence. American Journal of Psychiatry, 122(5), 509–522.</p></li><li><p>Loomer, H. P., Saunders, J. C., & Kline, N. S. (1957). Iproniazid, an amine oxidase inhibitor, as an example of a psychic energizer. Congressional Record, 1382–1390.</p></li><li><p>Moncrieff, J., Cooper, R. E., Stockmann, T., Amendola, S., Hengartner, M. P., & Horowitz, M. A. (2022). The serotonin theory of depression: a systematic umbrella review of the evidence. Molecular Psychiatry, 28(8), 3243–3256.</p></li><li><p>Janssen Pharmaceuticals / Johnson & Johnson. (2019, March 5). FDA approves Spravato (esketamine) nasal spray for treatment-resistant depression [Press release].</p></li><li><p>Yang, Y., Cui, Y., Sang, K., Dong, Y., Ni, Z., Ma, S., & Hu, H. (2018). Ketamine blocks bursting in the lateral habenula to rapidly relieve depression. Nature, 554, 317–322.</p></li><li><p>Lyu, D., et al. (2023). Sustained antidepressant effect of ketamine through NMDAR trapping in the LHb. Nature, 622, 802–809.</p></li></ol><p><strong>📬【联系我们】</strong></p><p><a target="_blank" rel="noopener noreferrer nofollow" href="">联系我们：zyx3200@163.com</a></p><p>微信：atgcdoctorschat，备注「加听友群」</p><br><a href="https://oia.xiaoyuzhoufm.com/player/6a1e766bac7bdb080c34b214?openTranscript=true&utm_source=rss&as=cHQ9MTIyNjE5MjQ3JmN0PXJzcyZtdD04&autoOpen=false">在小宇宙查看该单集文稿</a>
May 17, 2026
我们为什么相爱？失恋为什么那么痛？| 520 特辑
<p>这期节目的起点是人类学家 Helen Fisher 的著作《我们为什么相爱》，我们打开大脑，问一个更底层的问题：当我们爱上一个人，神经里究竟发生了什么？</p><p>原来，浪漫爱的底层驱动不是快乐，而是渴望——多巴胺的工作是让你"想要"，而不是让你"享受"。分手时经历的不只是情绪，而是真实的戒断反应，包括身体上的疼痛。</p><p>你会在这期听到：草原田鼠和山地田鼠为什么是动物界的"模范夫妻"和"渣男"？间歇性随机奖励为什么比稳定的爱更容易上瘾？以及失恋后为什么"越想停止反思、越停不下来"？</p><hr><h3><strong>【时间轴】</strong></h3><p>[<a class="timestamp">02:45</a>] 爱情的三种形式：性欲、浪漫爱、依恋</p><p>[<a class="timestamp">03:30</a>] 我们从田鼠身上学到了什么？</p><p>[<a class="timestamp">08:14</a>] 浪漫爱的底色是焦虑？</p><p>[<a class="timestamp">18:22</a>] 爱情真的是毒品吗？</p><p>[<a class="timestamp">25:06</a>] 什么样的爱更让人最上瘾？</p><p>[<a class="timestamp">28:59</a>] 分手为什么那么痛？</p><p>[<a class="timestamp">37:54</a>] 不要责怪自己</p><p>[<a class="timestamp">40:39</a>] 彩蛋：丘比特住在哪里？</p><p></p><p><strong>【节目中提到的书和播客】</strong></p><p><strong>《我们为什么相爱》</strong> Helen Fisher 著，英文原名 Why We Love: The Nature and Chemistry of Romantic Love。</p><p><a target="_blank" rel="noopener noreferrer nofollow" href="https://www.xiaoyuzhoufm.com/podcast-topic/6544f9efde390991a4a8288f?s=eyJ1IjogIjYwNzNjM2EwZTBmNWU3MjNiYjJmMmM1YiJ9">翻转电台 <strong>《爱的阶梯（会饮篇）》</strong></a></p><p><strong>📬【联系我们】</strong></p><p><a target="_blank" rel="noopener noreferrer nofollow" href="">联系我们：zyx3200@163.com</a></p><p>微信：atgcdoctorschat，备注「加听友群」</p>
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