从古老中药寻找癌症治疗新机遇

今年3月，耶鲁大学官网刊登了一篇题为《从古老中药寻找癌症治疗新机遇》的文章，讲述了该校科研团队以中医传统名方黄芩汤为基础，研制出抗癌药YIV-906的过程。

https://news.yale.edu/2020/03/13/ancient-chinese-medicine-unlocks-new-possibilities-cancer-treatment

More than 20 years ago, Yale pharmacology professor Yung-Chi Cheng, a leader in drug development for hepatitis B, cancer, and HIV, had a radical idea: What if he could unlock the therapeutic potential of ancient Chinese medicines for treating cancer? What if he could design botanical drugs that would make traditional cancer treatments work better?

20多年前，耶鲁大学药理学Henry Bronson讲席教授，治疗乙肝、癌症和艾滋病的中草药开发的领军人物郑永齐（Yung-Chi Cheng）有一个大胆的想法：是不是能发现古老中医药治疗癌症的潜力？是不是可以研发植物药，使癌症的传统治疗效果更好呢？

No one had done it before. The Food and Drug Administration didn’t even have a process in place for approving multi-ingredient botanical drugs, and wouldn’t until 2004, when the agency released botanical drug-specific guidelines.

以前没人做过这方面的研究。美国食品和药品管理局（FDA）一直都没有批准多成分植物药的相关程序，直到2004年该机构才发布了植物药专用指南。

Fellow researchers and drug development experts advised him to change course. Developing botanical drugs was too complicated, they said, too risky.

其他研究人员和药物开发专家建议他改变路线。他们说，开发植物药物太复杂，太冒险。

But the idea had taken hold, and Cheng, the Henry Bronson Professor of Pharmacology at Yale School of Medicine, was not going to let it go.

但这个想法始终萦绕在郑教授心头不曾放弃。

“Chinese medicine works by taking advantage of multiple chemicals, but also the capability of different organs in metabolizing these chemicals,” he said, surrounded by careening stacks of paper in his office at Yale’s Sterling Hall of Medicine. “It’s a totally new paradigm. I’ve been met with a lot of suspicion, but I think the results will speak for themselves.”

“中医不仅利用多种化学物质，还利用不同器官代谢这些化学物质的能力，”在耶鲁大学斯特林医学大楼的办公室里他说到，“这是一种全新的模式。我遇到了很多怀疑，但我认为结果会说明一切。”

All they need now are larger data sets. When the results of the international trial are available about three years from now, YIV-906 may find itself next in a long line of breakthrough drugs developed from natural products, a lineage that includes aspirin (from willow bark); Taxol (from pacific yew tree bark); Tamiflu (from star anise); and Artemisinin, a malaria treatment developed from the Chinese herb Artemisia annua, the discovery of which led to a Nobel Prize for chemist Youyou Tu.

现在，是癌症研究的一个里程碑式的时刻。郑教授和他的研究伙伴们正在为一种植物药YIV-906进行第一次国际临床试验。该试验的对象为肝癌和乙型肝炎患者。这项试验将在美国和中国的20个机构进行，包括纽约的纪念斯隆·凯特林癌症中心，诺斯威尔健康癌症研究所，中国国家癌症中心，台北医科大学和香港的玛丽女王医院。

“He is a pioneer,” said Jon Soderstrom, managing director of Yale’s Office of Cooperative Research, who began advising Cheng in 1996. “He is Lewis and Clark going into the Pacific Northwest without a map. By the sheer force of his personality and his empirical results, he made people pay attention to this space.”

“他是一个先驱，”耶鲁大学合作研究办公室主任乔恩·索德斯特罗姆(Jon Soderstrom)说，他从1996年开始为郑提供咨询。“他就像是路易斯和克拉克，在没有地图的情况下进入太平洋西北地区。凭借他的人格魅力和实证结果，让人们注意到了这一领域。”

Major drug companies are watching Cheng’s progress from the sidelines for now, said Shwu-Huey Liu, who began working in Cheng’s Yale lab as a postdoctoral researcher in 1993, when his focus was on antivirals and traditional anticancer drugs. “They monitor us and come to meetings,” she said, “but until we get approved, big pharma is not going to jump in.”

刘淑慧（Shwu-Huey Liu）从1993年开始在郑的耶鲁实验室做博士后研究，当时他的研究重点是抗病毒药物和传统抗癌药物。说，目前主要的制药公司都在关注郑教授的进展。“他们会参加会议和跟踪进度，”她说，“但在我们获得批准之前，大型制药公司是不会介入的。”

Today Liu is cofounder and chief scientific officer of Yiviva, Cheng’s biotech company, which is developing YIV-906. Combining Chinese and Spanish words, Yiviva translates as “long live medicine.” It’s a fitting slogan for a company that has resurrected an 1,800-year-old formula for stomach ailments to help fight cancer.

刘淑慧现在是郑教授的医起医药科技有限公司（Yiviva）的联合创始人和首席科学官。该公司正在开发YIV-906。“Yiviva”结合了中文和西班牙文，翻译为“长寿药”。这个名字贴切地描述了公司的使命。该公司已经复活了一个1800年前治疗胃病的配方，以帮助对抗癌症。

Old discoveries made new

老发现的新成就

In 1997, as Liu was finishing her postdoctoral work, Cheng mentioned his interest in Chinese medicine. “He said he thought it could be the future of medicine — especially in cancer,” Liu said. She was a chemist with no background in Chinese medicine, but “he thought we could work together,” she said. “My chemistry could help with quality control.”

1997年，刘淑慧完成她的博士后工作时，郑教授提到了他对中医的兴趣。他认为这可能是医学的未来——特别是在癌症方面。刘淑慧是没有中医背景的化学家，但郑教授认为他们可以一起工作。刘淑慧的化学专业知识有助于药物研究质量控制。

Liu connected with a librarian at Yale’s Sterling Memorial Library, and was led to a tucked-away room on the third floor where few patrons ever set foot. She spent hours leafing through Sterling’s collection of ancient Chinese texts, tracing the properties of Chinese herbs. Cheng had told her to look for herbs that were still in use, were not too rare, and had four or fewer elements.

刘淑慧与耶鲁大学斯特林纪念图书馆的一名图书管理员联系，在三楼一间隐蔽、少有人涉足的房间里，花了很多时间翻阅斯特林图书馆收藏的中国古代文献，寻找关于中草药特性的内容。郑教授告诉她要找那些还在使用的方剂，它们不太稀有，并且含有不多于四种元素。

Liu returned with about 20 formulations. One of them, an 1,800-year-old treatment for stomach ailments, was called Huang Qin Tang. It combined licorice, dates, peonies, and skullcap, and was traditionally prepared as a tea. After lab testing, the Cheng team found that Huang Qin Tang had a high inhibitory property against the debilitating side effects of a chemotherapy drug called CPT-11 (later approved as irinotecan), including diarrhea, nausea, and vomiting. Cheng and team developed a drug based on the formula and tested it on one thousand mice.

刘淑慧找到了大约20种配方。其中一种是1800年前治疗胃病的方剂，名叫黄芩汤。配方包括甘草、大枣、芍药和黄芩，当时被制成茶汤饮用。在实验室测试后，郑教授团队发现黄芩汤对一种名为CPT-11（后来被批准为伊立替康）的化疗药物的副作用有很强的抑制作用，包括腹泻、恶心和呕吐。郑教授和他的团队根据这个配方开发了一种药物，并在1000只小鼠身上进行了测试。

Not only did their drug, YIV-906, reduce the toxic GI side effects of the chemo drug, but it also enhanced irinotecan’s anti-tumor activity — a major discovery that revealed YIV-906’s powerful therapeutic potential.

他们研发的药物YIV-906不仅降低了化疗药物的毒性胃肠道副作用，还增强了伊立替康的抗肿瘤活性——这一重大发现揭示了YIV-906强大的治疗潜力。

“It was a surprise to us to see not only a reduction in the GI side effects of chemo but also an increase in the chemo action against tumors,” Cheng said.

“我们惊讶地发现化疗后不仅胃肠道副作用减少了，而且对肿瘤的化疗作用也增加了，”郑教授说。

The rise of “WE” medicine

“WE”医学的兴起

What followed were years of additional testing of the drug’s effectiveness for a range of cancers — including liver, pancreatic, and colorectal — in multiple human studies involving over 200 patients. The positive effects were replicated again and again. YIV-906 not only diminished the side effects of chemo drugs and radiation therapy, but also led to a stabilization of cancer, faster recovery, and longer survival rates.

之后的几年时间里，超过200名患者参加的临床试验，测试了该药对一系列癌症（包括肝癌、胰腺癌和结直肠癌）的疗效。积极的效果被一次又一次地验证。YIV-906不仅减少了化疗和放疗的副作用，而且使癌症病情更稳定，恢复更快，生存率更高。

In 2019, Cheng and his research partners ran a study with Yale immunobiology professor Lieping Chen to test YIV-906’s effectiveness with Chen’s immunotherapy drug anti-PD1, and found that YIV-906 enhanced the immunotherapy drug’s anti-tumor property. The combination of the drugs not only eradicated all tumors in mice, but when new tumors were implanted, the tumors did not grow. This suggested that YIV-906 with anti-PD1 “created a tumor-specific vaccine-like effect,” they wrote in their study.

2019年，郑教授和他的研究伙伴与耶鲁大学免疫生物学教授陈立平一起做了一项研究，测试YIV-906与陈教授的免疫治疗药物anti-PD1联合使用的疗效。测试结果发现，YIV-906增强了免疫治疗药物anti-PD1的抗肿瘤性能。这两种药物的结合不仅清除了小鼠体内的所有肿瘤，而且当小鼠被植入新的肿瘤时，肿瘤也没有成长。他们在研究报告中写道，这表明YIV-906与anti-PD1 结合后“产生了一种肿瘤特异性的类似疫苗的效果”。

They called the new approach “WE” medicine, a melding of Western medicine — focused on microscopic and single-disease targets — and Eastern medicine, exemplified by traditional Chinese therapies.

他们把这种新的方法称为“WE”医学，一种融合了西方（Western）医学——专注于微观和单一疾病和东方（Eastern）医学——体现了传统中医疗法的医学。

A whole-system approach is needed to combat a complex adversary like cancer, Cheng said.

“The reason this drug works is because it has multiple chemicals which can work on multiple sites to alter the whole system of homeostasis,” he said. “It triggers both innate immunity as well as adaptive immunity within the cancer micro-environment.”

郑教授说，人类需要一个完整的系统方法来对抗像癌症这样的复杂对手。他说：“这种药物之所以起作用，是因为它含有多种化学物质，可以在人体内多个部位起作用，从而改变整个体内平衡系统。它在癌症微环境中既能激发先天免疫，也能激发适应性免疫。”

All they need now are larger data sets. When the results of the international trial are available about three years from now, YIV-906 may find itself next in a long line of breakthrough drugs developed from natural products, a lineage that includes aspirin (from willow bark); Taxol (from pacific yew tree bark); Tamiflu (from star anise); and Artemisinin, a malaria treatment developed from the Chinese herb Artemisia annua, the discovery of which led to a Nobel Prize for chemist Youyou Tu.

他们现在所需要的只是更大的数据集。大约三年后，当国际试验的结果公布时，YIV-906可能会成为下一个从天然植物中研发出的突破性药物，其中包括阿司匹林(从柳树皮中提取)；紫杉醇(来自太平洋紫杉树皮)；达菲(来自八角茴香)；还有青蒿素，一种从中国草药青蒿中开发出来的治疗疟疾的药物，化学家屠呦呦因此获得了诺贝尔奖。

It has been a long journey, but if Cheng and team are successful, it could yield a new approach for treating not only cancer, but for the prevention and treatment of age-related diseases and pulmonary diseases using adapted traditional Chinese medicine, Cheng said.

郑教授说，这是一个漫长的过程。但是如果他和他的团队成功了，使用调整后的传统中药不仅可以成为一种治疗癌症的新方法，而且可以成为预防和治疗老年性疾病和肺部疾病的新方法。

Said Soderstrom of Yale’s Office of Cooperative Research, “This is an untapped potential people hadn’t thought much about before.”

耶鲁大学合作研究办公室的索德斯特伦（Soderstrom）说：“这是一个尚未开发的潜在领域，人们之前还没有做过太多探索。”

Liu, who has stuck with Cheng since she first began studying in his lab over two decades ago, through multiple startups and lean times, said his belief in the massive potential of botanical drugs has sustained her.

刘淑慧女士从20多年前开始在他的实验室学习以来，一路跟随，经历了多次创业和经济困难时期。是郑教授对植物药巨大潜力的信念支撑了她。

“Dr. Cheng said, ‘If we get the first Chinese medicine approved as an FDA prescription drug, it will change human history,’” Liu said. “And I believe him.”

郑教授说：“如果我们让第一例中药被FDA批准为处方药，它将改变人类历史，”刘淑慧说：“我相信他。”

附新华网《耶鲁大学教授郑永齐：中国成功抗疫“中药起了作用”》郑教授回答“您觉得中药的抗疫作用，怎样才能得到国际承认？”：

中药要想得到国际承认，必须在药材制备一致性、基于证据的临床疗效、药物作用机制和安全性等方面下功夫。