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A new angle on cancer

Visit the crested cactus garden during Biodesign C's grand opening Monday.
Cactus garden connects research inside the Biodesign Institute with its outside.
September 13, 2018

Crested cactuses inspire researchers at ASU's Biodesign Institute to look for new ways to control, not eradicate, the disease

Sun Tzu, the general of ancient China, wrote in his enduring military treatise “The Art of War” of the importance of knowing one’s enemy. The idea resonates strongly with Athena Aktipis, a scholar of many titles at Arizona State University who studies cooperation among living things.

While Sun Tzu’s enemies were on the battlefield, Aktipis’ are in the body.

“As an organism, we’re cooperation incarnate — the embodiment of cellular cooperation,” she said. “But it’s not a perfect system. Sometimes cells do mutate and stop cooperating. And that can sometimes lead to cancer.”

Cancer has been a part of life on Earth since the beginning of multicellularity, yet it is a foe humankind continues to grapple with — at least in part because we still do not fully understand it.

AktipisAthena Aktipis is an assistant professor in the Department of Psychology at Arizona State University and co-director of the Human Generosity Project, the first large-scale transdisciplinary project to investigate the interrelationship between biological and cultural influences on human generosity. and her husband, fellow ASU scholar Carlo MaleyCarlo Maley is an associate professor in the School of Life Sciences and a biologist who specializes in cancer, evolution and computational biology. He will lead the new Arizona Cancer and Evolution Center, to be established at ASU thanks to an $8.5 million grant from the National Cancer Institute., are making inroads toward a better understanding of the disease through more traditional scientific methods in their labs at the Biodesign Institute at ASU. But they’ve also conceived an unusual way to allow people to consider it anew.

Haunted by an idea 

About a decade ago, Aktipis was visiting Phoenix when she discovered crested cactuses, a phenomenon that results in some pretty wild-looking desert flora. Crested cactuses have a condition called fasciation, a mutation of their growth pattern that manifests in saguaros topped with bulbous, brain-like nodules and prickly pears that undulate like a flamenco skirt in motion.

Intrigued, Aktipis shared her newfound fascination with Maley, who studies cancer from an evolutionary standpoint.

“I remember telling Carlo, ‘There’s something here. There’s something really important and interesting that these cacti can tell us, but I don’t know what it is yet,’” Aktipis said.

Crested cactus garden

Crested cactus have a condition called fasciation, a mutation of their growth pattern that results in some wild-looking desert flora. Photo by Jarod Opperman/ASU

The crested cactuses continued to haunt her until five years ago, when she and Maley were in Berlin with colleagues working on a paper about cancer across the tree of life, analyzing how the disease affects multicellular life — from humans to animals to plants.

Once again, Aktipis found herself musing on the mutated cactuses. At last, she felt she had begun to figure out what secrets they might have to divulge.

The plant’s disfigurement, Aktipis said, “lets you really see the kind of growth patterns that can result from these mutations in a way that you can’t see in an animal,” because humans’ stem cells are embedded all over the body, whereas plants’ stem cells are located at their growing tips.

What’s more, Maley said, “crested cacti are a beautiful example of how cancer can show up in plants but also be lived with” — in essence, making the cactus a fully embodied argument that “cancer doesn’t have to be a death sentence.”

Graphic of stem cell locations

During their time in Berlin, they met garden designer Caspian Robertson. The group batted around the idea of creating a garden, not only to showcase the plants’ peculiar charm but to drive discussion of how our society thinks about cancer.

Still, the timing just wasn’t quite right.

Finally, in 2014, Aktipis and Maley arrived at ASU, drawn to the university’s embrace of interdisciplinary research with a purpose. They found the environment — both intellectual and physical — to be just right.

‘Beautiful monsters’

Serendipitously, ASU’s Frankenstein Bicentennial Project, a celebration of the writing and publication of Mary Shelley’s 19th-century monster novel, was in full swing at the time. They jumped at the chance to submit their crested-cactus garden concept for inclusion.

“These cacti are beautiful monsters,” Aktipis said. “[They are] amazing, almost sculptural pieces of art. But at the same time they are mutated.”

With the help of Biodesign Scientific Research Curator Pamela Winfrey, they put together a proposal. Winfrey was initially hesitant to get involved because of traumatic memories of the cancer that killed her grandmother. But as the project gained momentum and more people signed on to help bring it to fruition, it became apparent just how many others had a personal connection to the disease, including Byron Sampson, ASU landscape architect on the project, who had a massive brain tumor removed just four years ago.

And then there was Aktipis; her mother passed away from cancer when she was just a teenager, having kept it a secret all the way up to her death.

Stories like hers, Aktipis said, are indicative of the need for a cultural shift in the way our society views cancer: as an insidious foe that must be blasted with powerful drugs, often at the expense of the patient’s overall health.

Instead of complete eradication, she and Maley are exploring ways of controlling the disease. They recently received a grant from the Arizona Biomedical Research Centre to begin clinical trials in breast cancer patients of a new type of treatment called adaptive therapy.

Adaptive therapy is a unique approach in which patients receive treatment only when tumors are growing. It is still a nascent practice but so far has shown promise in animal models and in a clinical trial of patients with prostate cancer.

Aktipis, whose namesake is the goddess of war, concedes that the technique seems to go against people’s intuitions about how to win a fight.

“But the rules of war don’t work the same in the body,” she said. (Interestingly, another nugget of wisdom Sun Tzu bestowed in his treatise was the advice to use force sparingly.) “Cancer cells can still grow back really rapidly in a way an army couldn’t ever do.”

A Pitchfunder campaign to support continued expansion of the garden launched Sept. 17.

The garden is located to the east of Biodesign buildings A and B on the Tempe campus, where Aktipis and Maley conduct their research. It will be on display during the Sept. 17 public unveiling of the new Biodesign C building, which will feature the world’s first compact X-ray free-electron laser, an innovative device that will allow researchers to peer deep into molecular structure to better understand — among other things — the cellular mechanics of diseases such as cancer. 

WATCH: Carlo Maley speaks on "Arizona Horizon" about the new Arizona Cancer and Evolution Center

Crested cactus garden

Photo by Charlie Leight/ASU Now

If you go

What: Grand opening of Biodesign C.

When: 9 a.m., with ceremonial speeches beginning at 9:30 a.m. The building will be open to the public for self-guided tours until 11:30 a.m.; there will be breakfast items at each stop.

Where: Southwest corner of University Drive and Rural Road, Tempe.

Top photo: A mutated prickly pear cactus outside the new Biodesign C building in Tempe features flamenco0-skirt-like pads. Photo by Charlie Leight/ASU Now
This story originally appeared in the fall issue of ASU Thrive magazine. 

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National Cancer Institute selects ASU to lead revolutionary research in cancer

ASU awarded cancer research grant to approach the disease in novel ways.
June 7, 2018

University joins consortium to advance understanding of cancer and its clinical management with interdisciplinary approach

Take that, cancer.

Arizona State University has been awarded more than $8.5 million over five years from the National Cancer Institute to establish the Arizona Cancer and Evolution Center. The grant will establish ASU as the hub of an international network of research scientists who are dedicated to understanding cancer in an entirely new way.

“The establishment of the Arizona Cancer and Evolution Center at ASU by the National Cancer Institute positions the university at the forefront of new discoveries through groundbreaking, interdisciplinary approaches,” said Sethuraman Panchanathan, executive vice president of Knowledge Enterprise Development and chief research and innovation officer at ASU. “The convergence of leading-edge theory in evolution and ecology and experimental research and verification paves the way for rapid advances in the fight against a tenacious disease that continues to pose a challenge to researchers everywhere.”

As a designated Cancer Systems Biology Center, the Arizona Cancer and Evolution Center (ACE) will be embedded in a large-scale initiative by the National Cancer Institute (NCI), helping to support their Cancer Systems Biology Consortium (CSBC).

ASU is one of only 13 research institutions nationwide to be selected as a research center in the consortium. ACE will bring together leading researchers from a number of institutions, including the University of Southern California; University of California, Santa Barbara; University of Zurich, Barts Cancer Institute at the Queen Mary University of London; the Institute of Cancer Research in London; the Huntsman Cancer Institute at the University of Utah; Stanford University; and North Carolina State University. ASU partners include the Biodesign Institute, Hugh Downs School of Human Communication, Beyond Center and the Department of Biomedical Informatics.

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Evolution is the theory of cancer. The new Arizona Cancer and Evolution seeks to advance fundamental understanding of cancer and its clinical management through the development and application of evolutionary and ecological models to cancer biology.

The National Cancer Institute’s ambitious network of CSBC centers bring together clinical and basic cancer researchers with physical scientists, engineers, mathematicians and computer scientists to tackle key questions in cancer biology from a novel point of view.

“Cancer is a complex disease and it challenges our traditional approaches, making it hard to predict tumor growth and drug response,” said Daniel Gallahan, deputy director of NCI’s Division of Cancer Biology. “Cancer systems biologists embrace that complexity and use many different types of data to build mathematical models that allow us to make predictions about whether a tumor will metastasize or what drug combinations will be effective.”

“There are great opportunities to use methods from evolution and ecology to improve prediction, prognosis and cancer therapy,” said Carlo Maley, a Biodesign Institute researcher and a professor in the School of Life Sciences, who will head the new center. “Cells in tumors are constantly changing and evolving — measures from evolution and ecology are ideally suited for capturing and quantifying those dynamics. Those dynamics often lead to treatment failure.

"Rather than aggressive efforts to eradicate cancer, which may accelerate the evolution of treatment resistance and resurgence of the tumors, we are learning how to manage cancers so that we can live with the disease but not die from it.”

Maley explains that “all multicellular forms of life are susceptible to cancer, including plants, fungi, and animals. We can discover novel approaches to preventing cancer in humans by studying how other organisms have evolved to prevent cancer. Viewing cancer through an evolutionary and ecological lens offers researchers and physicians profound new insights and tools for both studying and controlling cancer.”

ACE has been established with the recognition that at its core, cancer is a disease rigidly governed by the mechanisms of evolution. Decades of research in the fight against cancer have vastly expanded knowledge of the disease and significantly improved patient treatments and outcomes. Yet despite the labors of thousands of brilliant scientists and clinicians and billions of dollars of research investment, the disease continues to exact a devastating toll on society.

The center’s mission is to advance the fundamental understanding of cancer and its clinical management through the development and application of evolutionary and ecological models to cancer biology. Ongoing research efforts have shown that evolutionary and ecological theory can be used to distinguish low-risk from high-risk tumors, develop novel approaches to cancer prevention, predict long-term response to therapy, and discover the fundamental biology that drives cancer.

“The Biodesign Institute has pursued daring and revolutionary approaches to human health, particularly in the area of cancer biology," said Joshua LaBaer, executive director of the Biodesign Institute and director of the Biodesign Virginia G. Piper Center for Personalized Diagnostics. "Leveraging university-wide resources, as well as Biodesign’s particular strengths in applying evolutionary approaches to the puzzle of cancer, the Arizona Cancer and Evolution Center will advance the agenda of the New American University promoted by President Michael Crow, where real world issues of the highest priority are attacked through the most far-sighted and interdisciplinary techniques.”

The overall research themes of the CSBC Research Centers address important questions in basic cancer research, including the emergence of drug resistance, the mechanisms underlying cancer metastasis, the role of evolutionary and ecological processes in tumor progression, and the role of the immune system in cancer progression and treatment.

Research conducted at the Research Centers will focus on the analysis of cancer as a complex biological system. The interdisciplinary investigators of the consortium will integrate experimental biology with mathematical and computational modeling to gain insight into processes relevant to cancer initiation, progression and treatment options.

In addition to applying systems biology methods to gain important insight into cancer, each CSBC Research Center supports an outreach program to promote training in interdisciplinary science, disseminate important research findings to the community, and to engage the public in cancer systems biology research. The Arizona Cancer and Evolution Center is launching innovations in this space as well, including collaborations with artists and musicians to view cancer from new angles, museum exhibits, and the establishment of a cactus garden next to the Biodesign Institute that highlights how many organisms, including plants, can live with cancer (called fasciations).

Sage Bionetworks in Seattle serves as the CSBC Coordinating Center to facilitate data and resource sharing and collaborative scientific activities across the entities of the CSBC, which includes the nine research centers as well as two new research projects.

“The CSBC program encourages team science and promotes a multidisciplinary approach to studying cancer,” said Shannon Hughes, program director for the CSBC. “These approaches are critical to our ultimate goal of improving the lives of cancer patients.”

Research at the Arizona Cancer and Evolution Center or ACE is supported by the National Cancer Institute of the National Institutes of Health under Award Number U54CA217376. The content provided here is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Top photo: Carlo Maley will direct the new Arizona Cancer and Evolution Center. He is a researcher in the Biodesign Institute and ASU's School of Life Sciences. Photo by Biodesign Institute

Richard Harth

Science writer , Biodesign Institute at ASU