Pharmacologist V. Craig Jordan, a professor of Breast and Medical Oncology and Molecular and Cellular Oncology at The University of Texas MD Anderson Cancer Center who discovered selective estrogen receptor modulators and developed breakthrough breast cancer treatments, died June 9 at his home in Houston.
He was 76.
Known as the “father of tamoxifen,” Jordan showed that the drug, originally created to block estrogen and prevent pregnancy, could stop the hormone’s ability to unlock tumor cells and cause cancer.
Jordan gave the failed contraceptive a second chance as a breast cancer treatment, saving the lives of millions of women around the world. Tamoxifen remains one of the world’s most successful cancer drugs and is on the World Health Organization’s list of essential medicines.
“Dr. Jordan leaves behind a remarkable legacy that will continue to influence cancer research and treatment for generations to come,” Peter WT Pisters, president of MD Anderson, said in a statement. “Craig’s passing is a profound loss to the scientific community and all those who had the privilege of knowing and working with him.”
Born in New Braunfels, TX, Jordan held dual American and British citizenship. He was the Dallas/Ft. Worth Living Legend Chair for Cancer Research at MD Anderson.
Dr. Jordan leaves behind a remarkable legacy that will continue to influence cancer research and treatment for generations to come.
Peter WT Pisters, MD Anderson
Jordan was recruited to the institution in 2014, after occupying positions at the University of Leeds, Switzerland’s Ludwig Institute, the University of Wisconsin-Madison, Northwestern University, Fox Chase Cancer Center, and Georgetown University.
In 1969, Jordan completed an undergraduate degree in pharmacology at the University of Leeds in West Yorkshire, UK. Four years later, he completed his Ph.D. in pharmacology from the same university.
Jordan wrote his doctoral dissertation on tamoxifen, which had been developed to block estrogen and prevent pregnancy. When tamoxifen turned out to increase, rather than decrease, fertility in women, Jordan convinced the company to let him experiment with it as a treatment for breast cancer.
Invited by Michael Harper to work at the Worcester Foundation, the “home of the oral contraceptive,” Jordan found that Harper had left for Geneva, leaving the recent graduate on his own. “I don’t know anything!”
Harper was the co-patent holder of ICI’s experimental drug 46,474, which had failed as an oral contraceptive.
So, Jordan decided to work with what he had.
“‘Why don’t we turn ICI 46,474 into a breast cancer drug?’ There’s been one publication on that and it shows it’s as good as estrogen,” said Jordan, who was also a member of the U.S. National Academy of Sciences and the National Academy of Medicine and an honorary fellow of the Royal Society of Medicine.
ICI 46,474 would later come to become known as tamoxifen, and Jordan’s work would change the face of breast cancer prevention and treatment for the next 30 years.
Recently, Jordan published a scientific memoir, “Tamoxifen Tales: Suggestions for Scientific Survival” (The Cancer Letter, May 27, 2022).
In a 2022 oral history interview with the Cancer History Project, Jordan described the history of discovery of tamoxifen.
This conversation, along with a review and excerpt of his book, are available in this issue.
In 1977, Jordan discovered tamoxifen’s most potent metabolite with its strategic hydroxyl leading to the development of the FDA-approved, hydroxyl-containing SERMs, raloxifene, and bazedoxifene.
In 1987, Jordan showed that tamoxifen and keoxifene maintained bone density in ovariectomized rats and prevented mammary cancer. His research was rejected by osteoporosis journals as “anti-estrogens cannot build bone, only estrogens can.”
In 1990, he wrote “important clues have been garnered about the effects of tamoxifen on bones and lipids so it is possible that derivatives could find applications to retard osteoporosis or atherosclerosis.”
In 1992, Jordan’s data led to a clinical trial that confirmed tamoxifen prevents decreases in bone density. In 1994, keoxifene was renamed raloxifene. In 1999, raloxifene was proven to maintain bone density and reduce breast cancer incidence in postmenopausal women. Jordan chaired the breast cancer committee evaluating raloxifene for osteoporosis treatment.
Today, there are five FDA-approved SERMs (tamoxifen, raloxifene, toremifene, basedoxifene, ospemiphene) with discovery links to Jordan’s laboratory.
These medicines are now used for the treatment of all stages of breast cancer, breast cancer risk reduction in high-risk women, osteoporosis treatment, painful intercourse alleviation, and menopausal symptoms relief.
Very few mechanism-based groups of medicines have had such broad impact on society.
Dr. Jordan’s research of tamoxifen has led to improved survival rates in hormone receptor-positive breast cancer, reduction in the rate of breast cancer recurrence, and reduced the risk of developing breast cancer in high-risk individuals. Today more than 40% of women survive a breast cancer diagnosis.
Debu Tripathy, MD Anderson
“Thirty years ago, many women didn’t survive a breast cancer diagnosis,” said Debu Tripathy, chair of Breast Medical Oncology, said in a statement. “Dr. Jordan’s research of tamoxifen has led to improved survival rates in hormone receptor-positive breast cancer, reduction in the rate of breast cancer recurrence, and reduced the risk of developing breast cancer in high-risk individuals. Today more than 40% of women survive a breast cancer diagnosis.”
While at the University of Leeds, Jordan was inspired by his maternal grandfather’s wartime service and joined the Officers’ Training Corps, volunteering for courses in chemical and biological warfare. Because of his scientific background, he was recruited into the British Army’s Intelligence Corps, becoming the youngest captain in the service. Eventually, he joined the British Special Air Service, where he received weapons and intelligence training.
Throughout his career, Jordan received many honors. He was a fellow of the British Pharmacological Society and a member of the American Society for Pharmacological and Experimental Therapeutics.
He was elected to the National Academy of Sciences in 2009 and the National Academy of Medicine in 2017. Jordan received the Sir James Black Award from the British Pharmacological Society in 2015, the Endocrine Society’s Aurbach Award for Translational Research in 2018, and the American Society for Pharmacology and Experimental Therapeutics’ Reynold Spector Award in 2019.
In 2002, Queen Elizabeth II named him Officer of the Most Excellent Order of the British Empire for his work with tamoxifen and his services to international breast cancer research. In 2019, Queen Elizabeth II appointed him Companion of the Most Distinguished Order of St. Michael and St. George for services to women’s health, an honor that celebrates his discovery and development of SERMs.
“Dr. Jordan’s impact extended far beyond his scientific achievements. As an educator and mentor, he inspired and shaped the careers of countless young researchers, sharing his knowledge, passion, and unwavering dedication,” Gabriel Hortobagyi, professor of Breast Medical Oncology, said in a statement. “His compassionate nature made him a beloved figure among his colleagues and students, who remember him not only as an exceptional scientist but also as a kind and caring individual.”
Jordan is survived by two daughters, Helen Turner and Alexandra Noel, and five grandchildren.
