Credit: Robert Seale

提供者：罗伯特·西尔

The UK–US pharmacologist V. Craig Jordan devised the first targeted therapy in cancer when he discovered that tamoxifen and other compounds that selectively target oestrogen receptors could both treat and prevent breast cancer. When Jordan began his research in the early 1970s, combination chemotherapy was perceived as the only treatment able to kill cancer cells; his concept of a targeted and gentle approach seemed counter-intuitive.

英美药理学家克雷格·乔丹（V.CraigJordan）发现他莫昔芬和其他选择性靶向雌激素受体的化合物可以治疗和预防乳腺癌，从而设计了第一种针对癌症的靶向治疗方法。当乔丹在20世纪70年代初开始他的研究时，联合化疗被认为是唯一能够杀死癌细胞的治疗方法；他有针对性和温和的方法的概念似乎违反直觉。

Today, selective oestrogen receptor modulators (SERMs) are used to treat a range of conditions, from all stages of breast cancer to osteoporosis, and even symptoms of menopause. Jordan has died aged 76.Jordan’s work has had an enormous influence, particularly on the lives of women. Breast cancer is the second most common form of cancer, after lung cancer, with 2.3 million cases diagnosed globally in 2022.

今天，选择性雌激素受体调节剂（SERMs）被用于治疗一系列疾病，从乳腺癌的各个阶段到骨质疏松症，甚至更年期症状。乔丹去世，享年76岁。乔丹的工作产生了巨大的影响，特别是对女性的生活。乳腺癌是仅次于肺癌的第二大常见癌症，2022年全球诊断出230万例。

Osteoporosis is thought to affect around 500 million people worldwide. Women over the age of 50 are particularly at risk because menopause lowers oestrogen levels, decreasing bone density.Jordan was born in New Braunfels, Texas, in 1947, to an English mother and a US serviceman. She moved back to England with her son when he was three years old.

骨质疏松症被认为影响全球约5亿人。50岁以上的女性尤其危险，因为更年期会降低雌激素水平，降低骨密度。乔丹1947年出生于德克萨斯州的新布朗费尔斯，母亲是英国人，父亲是美国军人。儿子三岁时，她和儿子搬回了英国。

He went on to set up a chemistry laboratory in his childhood bedroom. His biology teacher let him use the school’s lab and teach biochemistry to other students. He also encouraged Jordan to go the University of Leeds, UK, where he would develop a lifelong fascination with oestrogen receptors. Working as a technician at ICI Pharmaceuticals (later part of AstraZeneca) in Alderley Park, Jordan met endocrinologist Arthur Walpole, who held the patent for ‘ICI 46,474’ — which became commercially available as tamoxifen in 1973..

他在童年的卧室里建立了一个化学实验室。他的生物老师允许他使用学校的实验室，并向其他学生教授生物化学。他还鼓励乔丹去英国利兹大学，在那里他将终身着迷于雌激素受体。乔丹在奥尔德利公园的ICI制药公司（后来是阿斯利康的一部分）担任技术员，遇到了内分泌学家亚瑟·沃尔波尔，他拥有“ICI 46474”的专利，该专利于1973年作为他莫昔芬上市。。

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妇女健康研究缺乏资金-这些图表显示了如何

After earning his doctorate in 1972, Jordan, on Walpole’s advice, went to the Worcester Foundation for Experimental Biology in Shrewsbury, Massachusetts, which studied birth-control pills. ICI 46,474 proved to be an ineffective contraceptive; instead, he explored its potential as a breast cancer drug.

1972年获得博士学位后，乔丹在沃尔波尔的建议下，前往位于马萨诸塞州什鲁斯伯里的伍斯特实验生物学基金会研究避孕药。ICI 46474被证明是一种无效的避孕药；相反，他探索了它作为乳腺癌药物的潜力。

Using a rat model, Jordan discovered that it halted the growth of tumours with oestrogen receptors.At the Worcester Foundation, he met biochemist Angela Brodie, and inspired her to also develop a targeted anti-oestrogenic therapy, which works by blocking the enzyme responsible for oestrogen synthesis, aromatase.

使用大鼠模型，乔丹发现它阻止了雌激素受体肿瘤的生长。在伍斯特基金会，他遇到了生物化学家安吉拉·布罗迪，并激励她也开发了一种靶向抗雌激素疗法，该疗法通过阻断负责雌激素合成的酶芳香化酶起作用。

Selective aromatase inhibitors are now used worldwide to treat breast cancer in postmenopausal people. Connections Jordan made in Worcester also kick-started the process of obtaining FDA approval for tamoxifen, achieved in 1977.ICI launched tamoxifen to treat late-stage breast cancer in the United Kingdom in 1973.

选择性芳香化酶抑制剂目前在世界范围内用于治疗绝经后人群的乳腺癌。乔丹在伍斯特建立的联系也启动了获得FDA批准他莫昔芬的过程，该过程于1977年实现。1973年，ICI在英国推出他莫昔芬治疗晚期乳腺癌。

Jordan went back to Leeds as a lecturer in 1974. With funding from ICI, he explored the drug’s role in preventing both the occurrence and the recurrence of early-stage breast cancers. His experiments suggested that treatment over years rather than months produced better outcomes. The medical community was slow to be convinced, but large-cohort trials confirmed that 10 years of tamoxifen treatment in early-stage breast cancer reduced the risk of relapse by 30% and of related mortality by 48%.In 1977, Jordan found that a metabolite of tamoxifen, 4-hydroxytamoxifen, was even more potent.

乔丹于1974年回到利兹担任讲师。在ICI的资助下，他探索了该药物在预防早期乳腺癌发生和复发方面的作用。他的实验表明，多年而不是几个月的治疗产生了更好的结果。医学界很难相信，但大型队列试验证实，早期乳腺癌接受他莫昔芬治疗10年，复发风险降低了30%，相关死亡率降低了48%。1977年，乔丹发现他莫昔芬的代谢产物4-羟基他莫昔芬甚至更有效。

This opened the door for the synthesis of new SERMS, such as raloxifene, bazedoxifene and lasofoxifene.In 1980, Jordan joined the Carbone Cancer Center at the University of Wisconsin–Madison, and he was a full professor by the time he left in 1991. There, he found that tamox.

这为合成新的SERM打开了大门，例如雷洛昔芬，巴泽多西芬和拉索非芬。1980年，乔丹加入了威斯康星大学麦迪逊分校的卡本癌症中心，1991年离开时，他是一名全职教授。在那里，他发现了塔莫克斯。

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From 2005, Jordan held leading positions in cancer pharmacology at various US universities and hospitals. He continued to elucidate the complex mechanisms behind SERMs. He established a collection of breast cancer cell lines derived from patients, and freely shared it with other scientists.In 2015, he joined the University of Texas MD Anderson Cancer Center in Houston.

从2005年开始，约旦在美国各大学和医院的癌症药理学领域占据领先地位。他继续阐明SERM背后的复杂机制。他建立了一系列源自患者的乳腺癌细胞系，并与其他科学家免费分享。2015年，他加入了位于休斯顿的德克萨斯大学MD安德森癌症中心。

There, he unravelled how oestrogen can prompt the self-destruction of breast cancer cells in women who have been oestrogen-deprived for at least five years. He showed that drugs that mimic oestrogen, but avoid its side effects, might therefore be better for people for whom other therapies have failed.Jordan had a strong sense of service.

在那里，他揭示了雌激素如何促使被剥夺雌激素至少五年的女性乳腺癌细胞自我毁灭。他表明，模仿雌激素但避免其副作用的药物可能因此对其他疗法失败的人更好。乔丹有强烈的服务意识。

Inspired by his ex-military grandfather, he joined the officer-training corps while a student at Leeds, and took training courses in nuclear, biological and chemical warfare defence. Before completing his PhD, he was recruited to the UK Intelligence Corps, becoming the youngest captain in the service.

受前军事祖父的启发，他在利兹读书时加入了军官训练队，并参加了核、生物和化学战防御方面的训练课程。在完成博士学位之前，他被招募到英国情报局，成为该部队最年轻的队长。

He was a reservist for the UK Special Air Service, responsible for advising both the UK and US armies on chemical and biological defence.Among many other honours, in 2019, the late Queen Elizabeth II appointed Jordan the Most Distinguished Order of Saint Michael and Saint George for his services to women’s health.

他是英国特种航空队的预备役军人，负责为英国和美国军队提供化学和生物防御方面的建议。。

The world knows Jordan as a trailblazer in women’s health, but those of us who worked closely with him remember him as a down-to-earth scientist who exuded playfulness, kindness and inventiveness..

全世界都知道乔丹是女性健康领域的开拓者，但我们这些与他密切合作的人都记得他是一位脚踏实地的科学家，他散发着嬉戏、善良和创造性。。