Early Days at Duke

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.

A Triple Threat

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.

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.”

Legacy

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.