Game theory suggests more efficient cancer therapy

April 23, 2020

ITHACA, N.Y. - Cancer cells not only ravage the body - they also compete with each other.

Cornell mathematicians are using game theory to model how this competition could be leveraged, so cancer treatment - which also takes a toll on the patient's body - might be administered more sparingly, with maximized effect.

Their paper, "Optimizing Adaptive Cancer Therapy: Dynamic Programming and Evolutionary Game Theory," published April 22 in Proceedings of the Royal Society B: Biological Sciences.

"There are many game theoretic approaches for modeling how humans interact, how biological systems interact, how economic entities interact," said the paper's senior author, Alex Vladimirsky, professor of mathematics in the College of Arts and Sciences. "You could also model interactions between different types of cancer cells, which are competing to proliferate inside the tumor. If you know exactly how they're competing, you can try to leverage this to fight cancer better."

Vladimirsky and the paper's lead author, doctoral student Mark Gluzman, collaborated with oncologist and co-author Jacob Scott of the Cleveland Clinic. They used evolutionary game theory to model the interactions of three subpopulations of lung cancer cells that are differentiated by their relationship to oxygen: glycoltyic cells (GLY), vascular overproducers (VOP) and defectors (DEF).

In this model, previously co-developed by Scott, GLY cells are anaerobic (i.e., they do not require oxygen); VOP and DEF cells both use oxygen, but only VOP cells are willing to expend extra energy to produce a protein that will improve the vasculature and bring more oxygen to the cells.

Vladimirsky likens their competition to a game of rock, paper, scissors in which a million people are vying against each other. If the majority of participants choose to play rock, a greater number of players will be tempted to switch to paper. As the number of people switching to paper increases, fewer people will play rock and many more will shift to playing scissors. As the popularity of scissors grows, rock will become an attractive option again, and so on.

"So you have three populations, three competitive strategies, undergoing these cyclic oscillations," said Vladimirsky, who directs the Center for Applied Mathematics. "Without a drug therapy, the three subtypes of cancer cells may follow similar oscillating trajectories. Administering drugs can be viewed as temporarily changing the rules of the game.

"A natural question is how and when to change the rules to achieve our goals at a minimal cost - both in terms of the time to recovery and the total amount of drugs administered to the patient," he said. "Our main contribution is in computing how to optimally time these periods of drug treatment adaptively. We basically developed a map that shows when to administer drugs based on the current ratio of different subtypes of cancer."

In current clinical practice, cancer patients typically receive chemotherapy at the highest dosage their body can safely tolerate, and the side effects can be harsh. In addition, such a continuous treatment regimen often leads the surviving cancer cells to develop drug resistance, making further therapy far more difficult. The team's paper shows that a well-timed "adaptive" application could potentially lead to a patient's recovery with a greatly reduced amount of drugs.

But Vladimirsky cautions that, as is often the case in mathematical modeling, reality is much messier than theory. Biological interactions are complicated, often random, and can vary from patient to patient.

"Our optimization approach and computational experiments were all based on a particular simplified model of cancer evolution," he said. "In principle, the same ideas should also be applicable to much more detailed, and even patient-specific, models, but we are still a long way from there. We view this paper as a necessary early step on the road to practical use of adaptive, personalized drug-therapy. Our results are a strong argument for incorporating timing optimization into the protocol of future clinical trials."
The research was supported by the National Institutes of Health Case Comprehensive Cancer Center; National Cancer Institute; the Simons Foundation; the National Science Foundation; and the Chinese University of Hong Kong, Shenzhen.

Cornell University

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to