“All Tumors Great and Small”
When a Galapagos tortoise suffering from sarcoma needed help in 1983, zookeepers at the Staten Island Zoo called Mark Dewhirst, DVM, PhD, a young scientist at the University of Arizona who had been conducting clinical trials on dogs using radiotherapy.
They were hoping radiotherapy might also help the tortoise — named Jalopy because he scooted around with the aid of a skateboard contraption after losing mobility from his many surgeries — so they shipped him Dewhirst’s way.
Dewhirst’s ingenuity in rigging up a system to treat the 80-year-old tortoise, a species he’d never treated before, lengthened the tortoise’s life and made headlines.
The grandson of farmers and the son of a science professor at University of Arizona who studied parasites in cattle, Dewhirst said he grew up around animals, first in Kansas and then in Arizona. He seemed to be destined for veterinary medicine.
After earning an undergraduate degree in chemistry from University of Arizona and doctorates in veterinary medicine (1975) and radiation biology (1979) from Colorado State University, he joined the faculty at University of Arizona. His research career spanned more than three decades, most of them at Duke.
Come the end of the semester, Dewhirst — now vice director for basic science at Duke Cancer Institute and professor of radiation oncology, biomedical engineering and pathology — says he’s hanging up his lab coat.
The Dewhirst Lab, which focuses on the tumor microenvironment, specifically as it relates to tumor metabolism and hypoxia and ways to improve treatment modalities, including hyperthermia, is shutting down.
Dewhirst, who turns 68 this month, and radiation oncologist James Oleson, MD, now retired, were recruited to Duke in 1984 from the University of Arizona for their work in hyperthermia, a cancer treatment whereby body tissue is exposed to high temperatures and cancer cells are sensitized to radiation and chemotherapy or killed.
At the time, Dewhirst was also being recruited by Colorado State University and by the University of Wisconsin.
“It only took one trip for me to realize what a special place Duke is, and I do not regret that decision one bit,” he said. “Particularly impactful for me was the radiologic imaging capabilities here. Charlie Putman, PhD, who was chairman of the radiology department, was fantastic. I thought ‘we are coming here to start a hyperthermia program and we will have the capability of doing really important work with imaging that can interface with that’.”
Much of Mark Dewhirst’s knowledge about hyperthermia came from 30 years of canine comparative oncology research.
“Dogs are really good models for treating with hyperthermia because, unlike mouse tumors, you encounter the same challenges of trying to heat canine tumors that you do with human tumors,” he said. “I started my first trial in 1979 in Arizona and I continued to do them until my PO1 grant ran out of money in 2009 at Duke.”
While at Duke, Dewhirst has also conducted extensive work on oxygen transport and hypoxia (the deprivation of oxygen) in tumors.
“When I started in the field, the prevailing paradigm for why tumors become hypoxic was pretty simplistic,” he said. “It basically said that there are not enough vessels in the tumors and so the oxygen can’t diffuse far enough; it has a limited diffusion distance. I spent most of my career trying to understand what this really means. What we found was it’s a lot more complicated than that.”
Dewhirst authored and co-authored more than 100 papers on the subject of tumor hypoxia. Much of the clinical work was done with Duke radiation oncologist David Brizel, MD, who arrived to Duke a few years after Dewhirst.
“I consider him a colleague, a mentor and a friend,” said Brizel, who first met him when he was a junior resident at Harvard, “pummeling him with questions” after a talk Dewhirst gave on hyperthermia. “Then when I came down here to Duke I worked in his lab a couple days a week and helped him with some of his early work studying tumor microcirculation and developed a method for measuring the hematocrit in individual capillaries in mouse tumors using his window chamber model.”
Later the two of them published the first paper that showed that hypoxia in soft tissue sarcoma predicts for metastasis, which hadn’t been shown before.
“That kind of changed the paradigm because up until then people were thinking that hypoxia was just a problem for radiotherapy,” Dewhirst said. “The fact that it’s associated with metastasis means that it’s a bigger issue.”
While at Duke, Dewhirst also collaborated with David Needham, PhD, in the Pratt School of Engineering, to develop a novel thermally sensitive drug carrying liposome that was successfully translated to human clinical trials.
Dewhirst is finishing out his research career on cancer and exercise.
While there’s good epidemiological data, by other researchers, that shows that people that exercise regularly have a reduced lifetime risk for developing cancer, Dewhirst’s work is focused on how, post-cancer diagnosis, the combination of exercise with drug therapies or with radiation affect tumor physiology and treatment response.
A Triple Threat
You can take Dewhirst out of the lab, but you can’t take the lab out of Dewhirst.
He’s still fascinated with tumors.
“It’s my passion. It’s not going to stop when I retire,” he said. “I want to do some other things, but I don’t want to stop thinking.”
Dewhirst said that in his ‘retirement’ he’ll be working “about 60%” as much as he was before.
“I told my wife Nancy I’m looking forward to retiring,” he said. “I don’t want to work as hard as I have. It’s not that I’ve run out of ideas. I have lots of ideas. Now it’s time for the young dogs to go after that bone.”
In his retirement, Dewhirst plans to continue on as vice director for basic science at DCI; staying to help DCI director Michael Kastan, MD, PhD, with the competing renewal of the Cancer Center Core grant. He’ll also continue teaching in the Medical Physics program.
Kastan said his first introduction to Dewhirst was almost 20 years ago when he served on an NIH study section and reviewed one of Dewhirst’s grants.
“Beyond giving the grant a really good score, I looked forward to an opportunity to someday meet the clearly outstanding person who had written it,” said Kastan. “I am now honored to call Mark a friend and colleague. He is a true partner in running the cancer center and I cannot imagine where we would be without Mark in his role overseeing the DCI Shared Resources. He is one of those rare individuals who is a ‘triple-threat’ – great at science, teaching, and administration.”
In addition to his DCI position, Dewhirst plans to stay on as associate dean of faculty mentoring in the Duke School of Medicine that he’s held since the position’s creation in 2011 to enhance researchers’ success in obtaining grant funding and mentoring.
The coaching program he created, which has been used as a retention and recruitment tool by the School of Medicine, brings together three or four senior faculty with a lot of NIH study section experience with two to three more-junior applicants; helping them obtain DOD and NIH fellowships, K awards (individual training grants) and first R01 grants.
Dewhirst is proud of the results. In 2011, he said, the success rate for first-R01-applicants from Duke was around 9.8 percent. The current success rate is 27 percent. The national average for K award acceptance is around 30 percent but with Duke researchers, it’s 65 percent.
The office of Ann Brown, MD, MHS, the vice dean for faculty at Duke University School of Medicine, has been running that particular program since the end of January, while Dewhirst has turned his attention to “increasing appreciation for good mentorship” across the school.
He’s working part-time to develop mentoring resources through the Duke CTSA grant, a five-year, $47 million grant awarded to Duke in 2013 by the NIH as part of its Clinical and Translational Science Awards (CTSA) program. He organized a joint mentoring workshop with University of North Carolina at Chapel Hill in January targeted to all levels of faculty and researchers, and another one will be held in June. The plan is to replicate this three times a year.
A fellow in the AAAS and ASTRO, Dewhirst has well over 600 peer-reviewed publications, book chapters and reviews, with more than 28,000 citations. He also serves as a senior editor of Cancer Research and editor-in-chief of the International Journal of Hyperthermia. Despite scientific acclaim, he says mentoring is his “main legacy.”
“I’ve always liked mentoring. When I was a kid, people said I was bossy,” he laughed. “But, it is really that I love to help people learn things and to see them excel. It is just one of the greatest feelings to know that I had some kind of impact on my prior trainees. Many have and will go on to tremendous success themselves. I feel privileged to have had some part of that success. People will forget the papers I published, but they will not forget who I trained. It is a legacy that pays forward.”
He’s personally mentored several dozen graduate students, postdoctoral fellows, residents, junior faculty and medical students.
“My best students were those I learned more from than I ever taught,” Dewhirst said.
In addition to Brizel, his mentees at Duke include radiation oncology faculty members Greg Palmer, PhD; John Kirkpatrick, MD, PhD; and Janet Horton, MD; breast oncologist Kimberly Blackwell, MD, whom he helped get a K grant for research she conducted in his lab for five years; and biomedical engineer Nimmi Ramanujam, PhD. One of his trainees in canine comparative oncology, Mary-Keara Boss, DVM, PhD, is now a veterinary radiation oncologist at Colorado State University.
“Mark has served as a mentor to me since I joined the faculty in 2008,” said Horton. “He was kind enough to take me into his lab as a junior faculty, pair me with one of his post-docs, meet with me regularly to brainstorm and problem-solve, and generally provide invaluable support over the years as I worked towards becoming an independent translational breast cancer researcher.”
Horton added that she “benefitted from his years of basic laboratory experience as well as the credibility that comes with years of successful science.” And she said he taught her “the value of seeking out meetings with potential collaborators.”
Ramanujam, the founder of the Global Women’s Health Technologies Center at Duke, has worked with Dewhirst for 12 years. She said she “learned a ton about hypoxia and tumor biology, mentoring, the importance of research to patient care and how to have a good time.”
“Mark’s been instrumental in helping us develop innovative tools to study hypoxia and metabolism in living tumors,” Ramanujam said. “Most recently he’s used his expertise in tumor biology to help us design low cost therapeutics for cervical cancer and breast cancer in low resource settings as a surgical alternative.”
Gregory Palmer, PhD, an associate professor of radiation oncology, has also worked with Dewhirst for 12 years, including in his lab. A researcher with an engineering background, he now manages his own lab, the Palmer Lab.
“I learned alot from him about tumor biology and physiology and how to work together in a large multidisciplinary team and run a lab,” said Palmer. “Still, today, he’s the first person I go to when I have a problem. He’s a great listener and a great advocate and always has great advice.”
Many of his colleagues believe Dewhirst’s ‘retirement’ is up for debate.
“I am glad that Mark is only choosing to ‘slow down’ and not ‘retire’; Mark in slow-down mode is still a big plus for DCI and the institution,” said Kastan.
“I don’t think he knows how to be retired; his 60 percent is probably more than most people’s 110 percent,” laughed Brizel. “He’s just not replaceable. And you cannot say that about many people. My nickname for him was “the human synapse” because everyone he touches he creates a connection and a collaboration with. He’s gifted that way.”
When Dewhirst’s “five-year-plan” for easing into a full retirement is finished, the father of three boys and “a grandcat and granddog” will likely have more time for his hobbies — traveling (mainly Europe and Hawaii), reading (including autobiographies and crime novels), and hanging out at his beach condo. And he will join his wife Nancy, a retired nurse, in doing volunteer work with Urban Ministries.
He may also write his life story.
“I’m actually thinking of writing a memoir with a lot of focus on my years treating pets with cancer,” he said. A fan of the James Herriot books, he joked he’s going to call it ‘All Tumors Great and Small.’”
The Department of Radiation Oncology hosted the Mark Dewhirst Career Celebration at the JB Duke Hotel on June 10 and June 11, 2017. Guest speakers included among many others, Pierre Sonveaux, PhD, professor of Pharmacology and Therapeutics at the Université Catholique de Louvain; Albert van der Kogel, PhD, professor, Department of Human Oncology at the University of Wisconsin School of Medicine and Public Health; Chang Song, PhD, professor emeritus, Department of Radiation Oncology at the University of Minnesota; and Martin Brown, PhD, professor emeritus, Department of Radiation Oncology at Stanford University.
This article was originally published on the Duke Cancer Institute blog on May 8, 2017, and updated on June 11, 2017. The video was taped in May 2017.