The pharmacologist who revolutionized breast cancer treatment

British and American pharmacologist V. Craig Jordan discovered that tamoxifen and other compounds that selectively target estrogen receptors were effective in both treating and preventing cancer, devising the first targeted therapy for cancer. breast cancerWhen Jordan began his research in the early 1970s, combination chemotherapy was thought to be the only treatment capable of killing cancer cells. His concept of a targeted, gentle approach seemed counterintuitive. Today, selective estrogen receptor modulators (SERMs) are used to treat a variety of diseases, from all stages of breast cancer to osteoporosis and even cancer. Menopause SymptomsJordan died at the age of 76.

Jordan's research has had a profound impact on the lives of women in particular. Breast cancer is the second most common cancer after lung cancer, with 2.3 million cases diagnosed worldwide in 2022. Osteoporosis is thought to affect approximately 500 million people worldwide. Women over 50 are particularly at risk as menopause causes declining estrogen levels and reduced bone density.

Jordan was born in New Braunfels, Texas, in 1947 to a British mother and a US soldier. His mother returned to England with her son when he was three years old. Jordan built a chemistry lab in his childhood bedroom. His biology teacher gave Jordan access to the school's lab and taught biochemistry to other students. He also encouraged Jordan to attend the University of Leeds in England, where he developed a lifelong fascination with estrogen receptors. While working as an engineer at ICI Pharmaceuticals in Alderley Park (later a division of AstraZeneca), Jordan met Arthur Walpole, an endocrinologist who held a patent for ICI 46,474, marketed as tamoxifen in 1973.

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After completing her doctorate in 1972, Jordan followed Walpole's advice and went to the Worcester Foundation for Experimental Biology in Shrewsbury, Massachusetts to research contraceptives. ICI 46,474 proved ineffective as a contraceptive, but Jordan instead explored its potential as a breast cancer treatment. Using a rat model, Jordan found that it stopped the growth of tumors that had estrogen receptors.

At the Worcester Foundation, Jordan met biochemist Angela Brody, who inspired her to develop targeted anti-estrogen therapies that work by inhibiting aromatase, an enzyme in estrogen synthesis. Selective aromatase inhibitors are now used worldwide to treat postmenopausal breast cancer. The connections Jordan made at Worcester also helped lead to the FDA approval of tamoxifen in 1977.

ICI launched tamoxifen in the UK in 1973 for the treatment of late-stage breast cancer. Jordan returned to Leeds as a lecturer in 1974. With funding from ICI, he investigated the drug's role in preventing both the development and recurrence of early breast cancer. His experiments showed that treatment over years rather than months produced better results. The medical community was slow to convince, but a large cohort study confirmed that 10 years of tamoxifen treatment for early-stage breast cancer reduced the risk of recurrence by 30% and associated mortality by 48%.

In 1977, Jordan discovered that a metabolite of tamoxifen, 4-hydroxytamoxifen, was even more potent, paving the way 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, where he was a professor by the time he retired in 1991. There, he discovered that tamoxifen could promote the growth of endometrial cancer in some women, sounding the alarm about gynecological monitoring. In 1987, Jordan made another counterintuitive breakthrough by showing that raloxifene could preserve bone density in ovariectomized rats. This finding was initially rejected by all osteoporosis journals, but in 1999, a large-scale clinical trial vindicated him again (S.R. Cummings. other. JAMA 2812189–2197; 1999).

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Since 2005, Jordan has held leadership positions in cancer pharmacology at various universities and hospitals in the United States, where she has worked to elucidate the complex mechanisms behind SERMs. She established a collection of patient-derived breast cancer cell lines that she freely shared with other scientists.

In 2015, he joined the University of Texas MD Anderson Cancer Center in Houston, where he uncovered how estrogen prompts breast cancer cells to self-destruct in women who have been deprived of estrogen for at least five years. He showed that drugs that mimic estrogen but avoid its side effects might be better for people for whom other treatments have failed.

Jordan had a strong sense of service. Inspired by his grandfather, a former military man, he joined the Officer Cadet Corps while studying at Leeds University and undertook a training course in nuclear, biological and chemical warfare defence. Before completing his PhD he was recruited into the British Intelligence Corps, becoming the force's youngest ever captain. As a reservist for the Royal Special Air Service he was responsible for advising both the British and US military on chemical and biological defence.

Jordan has received many honours from Queen Elizabeth in 2019, including being made an Order of St Michael and St George for his services to women's health. The world knows Jordan as a pioneer in women's health, but those of us who worked closely with him remember him as a down-to-earth scientist with a sense of playfulness, kindness and inventiveness.

Competing interests

The authors declare that they have no conflicts of interest.