Evolution could hold the key to preventing cancer deaths
How an early career cancer researcher is studying cancer’s earliest appearance to unlock new areas of exploration
T-32 postdoctoral scholar Zach Compton works in a lab at the University of Arizona BIO5 building.
At a mere 16 years old, Zachary Compton got his first job in a cancer clinic in his hometown of Yuma.
He thought cancer was well on its way to being figured out, but he quickly discovered there are still many lives lost to the disease daily.
“It was a painful introduction into the cancer burden in Arizona,” said Compton, who is now a postdoctoral fellow in the U of A Health Sciences College of Medicine – Tucson. “My experience with those cancer patients at a young age instilled in me all the motivation I needed to push hard in my research.”
He plodded along a traditional path in cancer biology and cancer genetics during his undergraduate studies at Arizona State University. But his life changed in his senior year when he read about Carlo Maley, PhD, who received a large NIH grant to study cancer in elephants.
The elephant-cancer connection piqued Compton’s curiosity, and he contacted the ASU professor in the Center for Evolution and Medicine in the Biodesign Center for Biocomputation, Security and Society. At their first meeting, Maley made a simple statement that captivated Compton and drastically changed the course of his research interests.
“Maley told me, ‘We have a couple hundred million years of vertebrate evolution on this planet,” Compton said. “It's solved so many problems, such as the echolocation connection to sight and flight for bats. It's likely solved the problem of cancer in some way––We just haven't figured that out yet.’”
With the precision of a forensic scientist, Compton now investigates the evolutionary history of elephants and thousands of other vertebrates to track down the beginnings of cancer and mechanisms for suppressing the disease. He combines that with his focus on therapeutic resistance in late-stage tumors as a niche area of exploration with great potential for game-changing discoveries.
In the January issue of Cancer Discovery, Compton’s study on “Cancer Prevalence across Vertebrates” was featured on the cover. The team of researchers studied 16,049 animal necropsies from 292 vertebrate species. They found that cancer prevalence and somatic mutation rates increased in animals with a larger body mass but decreased in animals with a longer gestation time. The researchers also identified several outlier species that have abnormal tumors or masses called neoplasia.
“Our objective is to find out what we can learn, and most importantly, how we translate that to humans,” he said. “Even if you're doing research that seems somewhat disconnected, like cancer and elephants and other animals, knowing the population that you're trying to serve is important and motivating, quite frankly.”
Curing cancer starts with community
After completing his doctorate in evolutionary biology, Compton chose to stay in Arizona due to his strong network of collaborators, mentors and mentees and is now working in the lab of Koenraad Van Doorslaer, PhD, assistant professor in the U of A Animal and Comparative Biomedical Sciences and co-leader of the cancer center ‘s Cancer Biology Program. Compton’s innovative research is supported by the T32 Cancer Prevention and Control Postdoctoral Fellowship Program.
“The training grant provides a comprehensive program of professional development activities and one-on-on mentoring opportunities to prepare the next generation of cancer researchers to conduct high-impact research, like Zach’s,” said Gloria Coronado, PhD, the U of A Cancer Center’s associate director of population science and a professor at the U of A Mel and Enid Zuckerman College of Public Health.
Compton credits three of his T32 Health Disparities principal investigators for his success at U of A: Cynthia Thomson, Robin Harris, and Terry Badger, and the T32 program manager, Rebecca Crocker.
“My work is pretty far outside of the traditional approaches to cancer prevention, and I think they took a small gamble in bringing me into the T32 program, so I am very thankful it has paid the dividends it has,” Compton said. “Not only have I been able to be productive in the program, but the program principal investigators have really improved my work by coaching me on how to aim this research at cancer prevention.”
While completing his doctoral work, Compton co-founded and led the Arizona Cancer Evolution Scholars program to assist other students in getting experience and funding in the field. That program is still active and has assisted more than 100 students to study cancer and its evolutionary beginnings.
“Across the cancer center, I feel the motivation to pursue research that not only has a positive impact on cancer research but on those suffering, or have yet to suffer, here in Arizona,” Compton said. “It is of immense personal value to me that my work—whether in the community, training students, or cancer research—serves my neighbors.”
Finding the answer in evolution
Compton said that there are two truths about evolutionary history and the problem of cancer prevention. For one, people have a long evolutionary history with cancers’ genetic mechanisms, and the timescale of cancer’s history is difficult to conceptualize.
“The genes that prevent cancer in our body or those that are vulnerable to promote cancer have been around for the 100,000 years that modern humans have been around,” Compton said. “Several of these genes are so evolutionarily ancient, we find them in plants and fungi. Given this is the case, it's important for us to build our understanding of the function of these genes and how they impact our disease risk.”
The second truth, he said, is that humans, like all other animals, have some evolved risk of cancer that was shaped by the ecology and environment in which they evolved. That environment is much different than the environment in which the vast majority of humans today live.
“We call this an evolutionary mismatch,” Compton said. “By understanding more fully the evolution of humans, their close evolutionary relatives, and the environments in which they evolved, we can anticipate what about our modern environment may increase our cancer risk.”
Compton believes there will never be a singular cure for cancer, regardless of how good we become at treating it.
“Certainly, we will get better at curing individual patients, but it seems obvious to me the most headway we can make on lowering cancer deaths is through cancer prevention,” Compton said. “One of the more personal takeaways from my study of cancer across the tree of life is that it is very much part of the experience of life on earth.”