Friday, October 12, 2018

Physics and math bring more precision to treatment

By Suzie Siegel

Dr. Jeremy Mason
My mentor at a cancer conference has taken only one biology class in his life, and that was when he was a freshman in high school. Nevertheless, his knowledge can change the way you think of cancer — and the way doctors treat it.

“Math, physics and computer science have a profound impact on the field of cancer research today,” said Jeremy Mason, who has his doctorate in engineering. “Other scholars with little to no experience in cancer are applying their own knowledge and skills to build detailed and relevant models of the event prediction, cellular birth/death processes, therapeutic responses and much more.

“One day, these models will be used for the common goal of improving patient care and extending lives.”

Dr. Mason, assistant professor of oncology at the University of Southern California in Los Angeles, came from the heart of Cajun country and went to college in Georgia.

“I grew up in a region where diabetes, stroke, and heart attack were discussed more than cancer, so I started down this path with virtually no prior knowledge on the subject. Instead of having to correct any misconceptions I had, I was forced to learn everything from the ground up. Fortunately, since I was classically trained as an engineer, applying math and physics to cancer research allowed me to view the challenges that were arising within the field and helped to quantify the complexity in a manner that made sense to me.

“Cancer research has interested me in a number of ways. It presented a unique challenge that does not have a definitive solution, but has profound impact on numerous people. Both patients and their loved ones. Also, every day I get to work with some truly amazing people.”

Dr. Caligiuri with me
Dr. Mason works on the Convergent Science Initiative in Cancer with USC Professor Peter Kuhn, who has his doctorate in physics.  This is the second year that I won a scholarship to attend the American Association for Cancer Research’s annual meeting as part of its Scientist↔Survivor Program. Drs. Mason and Kuhn were the scientific mentors for the team I was on. We had to do a short presentation on math, physics and evolution in cancer research.

The meeting in April drew 22,500 participants to Chicago. The survivor program gives participants a chance to meet VIPs, such as Michael Caligiuri, MD, then president of AACR, in social settings. Dr. Caligiuri is president of the City of Hope National Medical Center in Duarte, Calif.

Dr. Shihong Zhang
Most doctors and scientists work on carcinoma. I always ask about their research: “Is this the same or different for sarcoma? How could this apply to sarcoma?”

Because sarcoma is rare, I could read the summaries of all the sarcoma research presented. For example, I met Shihong Zhang, PhD, who works on immunology at Fred Hutchinson Cancer Research Center in Seattle. She presented a poster on the use of interferon gamma radiation to heat up the cold microenvironment of synovial sarcoma and myxoid-round cell liposarcoma, both of which express the protein NY-ESO-1. The goal is to make them more susceptible to immunotherapy.

Dr. Jianguo Huang 
Jianguo Huang, PhD, of Duke University Medical Center in Durham, N.C., presented a poster on how long, noncoding RNA NEAT1 promotes lung metastasis in soft-tissue sarcoma.

“Metastasis is the major cause of death from cancers, including sarcomas,” said radiation oncologist David Kirsch, MD, PhD, principal investigator on the NEAT1 study. “We seek to understand how sarcomas spread from their primary site to other parts of the body, such as the lungs. By uncovering the way that sarcomas spread, we hope to develop new approaches for preventing or treating sarcoma metastasis.”

Dr. Kirsch, a Duke professor, thinks it would be a stretch to include this presentation in my topic. Dr. Kuhn did not.

Dr. Peter Kuhn
“Physicists are often trained as high-complexity problem solvers, a k a fancy plumbers with duct tape,” Dr. Kuhn said. “It is not necessarily just about light and energy but really just as much about the body as a complex system (space) that experiences many factors of evolution and lifestyle (time). Understanding this space-time complexity and starting to determine what we need to measure to predict it, is exactly what the physics and math guys are going after.”

“The same mechanisms that allow organisms to adapt and survive are the same mechanisms that cause cancer,” said pathologist Carolyn Compton, MD, PhD, a professor at Arizona State University in Scottsdale and chief medical officer of its Complex Adaptive Systems Institute.

Dr. Carolyn Compton makes a point
Cell mutations drive evolution, she said. They allow some animals to adapt and survive in their environment. But mutations also help cancer cells grow out of control in different environments in our bodies. Thus, humanity takes the bad (cancer) with the good (evolution).

Many people have cancer cells in their bodies, but they don’t know it because the cells haven’t found a hospitable environment in which to grow. It takes about a billion cancer cells to make a tumor that is 1 centimeter cubed, Dr. Compton said. The cells in a cancerous tumor may not be all the same, she said, and some may survive treatment.

“Cancer is the ultimate complex, adaptive system. It does new things that you did not expect. If we think of weather, there’s all this math modeling to make predictions, but we’re not there yet” in cancer research.

Sometimes treatment isn’t strong enough to kill cancer. Sometimes doses are stronger than they need to be, causing unnecessary damage to healthy cells, she said. Sometimes cancer treatment can cause so much damage that people develop new cancers.

Dr. Kuhn is working to develop liquid biopsies — blood samples that could make treatment more precise and predict a patient’s future. These samples would be more accurate in screening for cancers. They could predict which treatment would work for a patient, monitor the cancer for resistance to treatment, and predict what treatment might work if the cancer returns.

For many sarcoma patients, treatment can feel like a gamble. I'm glad that math and physics can give us better odds.

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