One would get little quarrel with the hypothesis that the development of “targeted therapy” is one of the most substantial advances in cancer care and cancer research over the past 50 years.
In fact, my colleague Eric Rosenthal and I recently conducted a poll, published in “Centers of the Cancer Universe,” of more than 100 cancer leaders and scientists, asking each what they judged to be the most important advances in cancer research since the signing of the National Cancer Act on Dec. 23, 1971.
Of the responses, 70% noted advances in immunology and the development of immune checkpoint inhibitors, 65% cited discoveries in genetics and genomics and the Human Genome Project, and 62% voted for the development of “targeted therapies” —the most frequently cited being receptor tyrosine kinase inhibitors (e.g., imatinib), monoclonal antibodies (e.g., trastuzumab).
Interestingly, tamoxifen was mentioned by only a few respondents. It is very easy to argue, however, that tamoxifen was one of the first targeted therapies, having been studied initially in the mid-1960s as a contraceptive; rather shortly after failing in that application was picked up and studied by a young British PhD student at Leeds University in the early 1970s, V. Craig Jordan.
While it is also true that antifolate agents and pyrimidine synthesis antagonists (aminopterin, methotrexate and 5-fluorouracil) deserve to be in the ranks of “targeted therapies” as their enzyme targets were characterized in the late 1950s and early 1960s, let us not quibble about what was the very first targeted anticancer therapy, and focus for the moment on the recently published book by Dr. Jordan, “Tamoxifen Tales: Suggestions for Scientific Survival.”
An excerpt of “Tamoxifen Tales: Suggestions for Scientific Survival” appears here in the Cancer History Project.
Craig Jordan tells the tale of his journey to become a highly accomplished and award-winning scientist. He outlines along the way his remarkable body of work, focusing on the development of tamoxifen as an agent used in the treatment and prevention of breast cancer.
Reflection on the work outlined in this book fully supports recognizing Dr. Jordan as the “father of tamoxifen,” and arguably the entire class of agents, which has become known as selective estrogen receptor modulators (SERMs).
Jordan tells the story of his scientific career starting at the very beginning—birth in New Braunfels, TX, his father a U.S. serviceman who, after participating in the Normandy landing, returned to marry the English woman he’d met who was serving as a fire service dispatcher near his training location outside London.
The couple moved to the U.S., but the marriage did not last, and Craig and his mother returned to England—first living with Craig’s mother’s parents in Wilmslow, East Cheshire.
Here, Craig’s mother made the acquaintance of Geoff Webster Jordan, whom she would marry a few years later. Mr. G.W. Jordan adopted Craig, ensuring him British citizenship. We are provided many details of Dr. Craig Jordan’s childhood and early education in Bramhall, Stockport England, leading up to university, and his PhD work at Leeds University.
Among many anecdotes and vignettes of his academic and scientific journey Jordan weaves two themes through his recounting of his accomplishments: (1) the importance of the commitment and teamwork of the members of his lab at each of the several institutions in which he worked (Leeds University, Worcester Foundation for Experimental Biology [WFEB], The University of Wisconsin Clinical Cancer Center, Northwestern University, Georgetown University, Fox Chase Cancer Center and MD Anderson Cancer Center)—his Tamoxifen Teams, and (2) An interesting “side story” of his interest in British military history and his military service.
Jordan picked up the trail of his tamoxifen tale starting with what turned out to be an abortive PhD project to isolate and crystalize the estrogen receptor (ER) bound to an ER antagonist (e.g., tamoxifen). This turned out to be an unattainable goal given the technology of the time.
Jordan, who for reasons never made clear in this work, had always had an affinity to do cancer research, turned his PhD thesis to a detailed analysis of the structure-activity relationships of the antiestrogens. This set him on a path to understand the pharmacology, biochemistry and the anti-breast cancer properties of these agents, particularly ICI 46,474 (tamoxifen).
In “Tamoxifen Tales,” Jordan outlines the journey of discovery which led to the enormous contribution that antiestrogens, especially tamoxifen have made to the improved treatment as well as the prevention of breast cancer.
Jordan was at the center of the evolving understanding of the pharmacology and biology of these agents, and his recounting emphasizes the important contributions of his lab teams, pointing out how he encouraged and supported the work of students and technicians in his group at each stop in his academic journey.
The last chapter in the book is unusual in that Jordan devotes it to the personal recounting by each of 19 PhD students and postdoctoral students, who worked with Jordan, their personal scientific work, and growth.
His tamoxifen team members often accompanied him through changes from one institution to another. Each of the selected tamoxifen team members has achieved substantial success in academic or pharmaceutical company leadership over the years.
A notable aspect of Jordan’s work with tamoxifen and other antiestrogens is the way the work was supported by Imperial Chemical Industries (ICI, later to become AstraZeneca) the pharmaceutical company who developed the drug and held its patents for many years.
ICI provided rats for animal studies and support for tamoxifen team members. Communication, support and coordination between Jordan and the leaders of the tamoxifen work at ICI was extensive and critical.
The accomplishments of V. Craig Jordan are remarkable. For his work in dissecting the pharmacology, molecular mechanisms, in vitro and in vivo activity of antiestrogen compounds, Dr. Jordan has received numerous U.S., British and international awards.
Reflection on the work outlined in this book fully supports recognizing Dr. Jordan as the “father of tamoxifen,” and arguably the entire class of agents, which has become known as selective estrogen receptor modulator.
The list of honors and recognitions really is too long to enumerate in this brief review; an attempt to summarize “the most important” runs the risk of misclassifying and offending one or more organizations, and Dr. V. Craig Jordan. Google Dr. Jordan or read the book.
The awards also include recognition for his service as a military officer, where he served, while a PhD student, as a captain in the Intelligence Service, whose expertise was nuclear, chemical and biologic warfare (with top secret clearance).
He was trained in the U.S. as a Drug Enforcement Agency Agent and finished his career in the British Special Air Service (paratrooper trained). The endorsements in the frontispiece of this book reflect Dr. Jordan’s broad experiences—from Oliver Sacks, MD Admiral Bill [sic] McRaven, as well as David Cornwall (a.k.a John le Carre’); the foreword is written by Melvyn Bragg, Lord Bragg of Wigton, Chancellor University of Leeds (1999-2017).
This book contains several “rules to live by and survive” in academic life. Based on Jordan’s success, they merit attention. It is also clear he has been very supportive of his students and postdoctoral fellows; I think he would say this has been one of his leading reasons for his success.
The story of tamoxifen is a very interesting one, one which evolved through Dr. Jordan’s work in an era when animal models and in vitro experiments were the key to dissecting mechanism. His recounting of work based on passage of human and animal breast cancer lines for decades is instructive.
Dr. Jordan’s story would have been enhanced had his publisher provided more editorial and proof-reading assistance. There is repetition of some anecdotes and stories and some punctuation and spelling errors that should not survive in 2022.
Perhaps the one that struck the reviewer most was the citation of the “ASCO Karnofski Award”—REALLY? It’s Karnofsky with a “y”—in the name of the Lord.
The story of tamoxifen advances would have been made clearer by improved graphics and figures of molecular structures.
But these are quibbles. The story is engaging, the accomplishments remarkable and highly impactful. Dr. Jordan has not only mentored his students and fellows, he has helped support their educational expenses on occasion and has endowed lectureships in former institutions important to his development.
Finally, I am disheartened by one of the early vignettes in this book: Craig recounts his own struggle with metastatic renal cell carcinoma. Four years and all the usual therapies with good but waning results. May the ongoing search for another effective approach bear fruit. V. Craig Jordan still has much to contribute!
Jordan will be signing copies of his book June 5 from 10:15–10:45 a.m. at the Elsevier booth at the ASCO annual meeting.