Paul Newton aims to change the way researchers and clinicians approach the treatment of cancerous tumors.
The USC Viterbi professor of aerospace and mechanical engineering and mathematics recently published a paper, in collaboration with Jeffrey West, Ph.D. AME ’17, that could lay the foundation for targeting interactions between cells as a way to control tumor growth.
Their article, titled “Cellular Interactions Constrain Tumor Growth” was published on February 5th, 2019 in the “Proceedings of the National Academy of Sciences.” The pair found that as tumor cells begin to communicate, the growth of the overall tumor slows. This is because when cells interact, they synchronize and begin to occupy similar niches in the body. Coupled cells then compete for the same resources, so growth will slow compared to a more diverse population of cells that make use of differing conditions, resources, and reactions. Newton’s model relates the growth conditions of the tumor on a level of individual cells to its overall growth within the body.
“We hope to lay a foundation for a new way to control tumor growth by targeting interactions between cells,” Newton said.
Newton and West’s paper is theoretical, based on mathematical models and computer simulations. No clinical trials have been attempted yet to test their ideas. Instead, they compare their theory to existing data and hope their model can help oncologists understand the connections between cell-to-cell interactions and overall tumor growth. A better understanding could then allow for the development of therapies that specifically target and disrupt the functional coupling of cells, as opposed to radiation or chemotherapy that target the maximal destruction of rapidly dividing cells.
A tumor is composed of a collection of cells occupying different, changing states. Cells within the tumor compete with surrounding cells for survival and prosperity within the microenvironment.
In the early stages of tumor growth, the state a cell occupies is independent of surrounding cells because cell-to-cell communication has not yet been established. The state of a cell is the variable in the mathematical model developed by Newton. In this early stage with limited intercellular communication, tumor growth has been observed to be exponential.
As the tumor grows, cells begin to transmit information to other cells by passing molecules and signals through gap junctions, the microenvironment, or the bloodstream. This communication causes cells to synchronize and become effectively coupled, instead of independent. As more cells occupy more similar niches, competition increases, and cell growth slows. As the tumor matures, the communication developing between cells increases and as a result, overall tumor growth is slowed — tumor growth slows down when the tumor becomes more homogenous.
Newton’s model takes advantage of this fact and proposes focusing on the functional coupling of cells, allowing natural competition between cells to slow tumor growth, instead of the more traditional focus on therapies that kill the maximum number of cells.
He is currently talking with other researchers in the field and giving seminars and lectures around the country on his mathematical model. He hopes to expose his ideas to other experts who can begin to design future clinical trials or identify existing therapies that could be used to target functional coupling of cells to control tumor growth.
West, a former Ph.D. student of Newton, is currently a post-doctoral scholar at the H. Lee Moffitt Cancer Center & Research Institute in Tampa, Florida. This past summer, Newton spent three months at the Moffitt Cancer Center with West, in the center’s Mathematical Oncology Department, to further develop their model. After working for several years on a variety of related ideas, Newton and West crystalized some of their key ideas in this new publication.
“It’s one thing to introduce a new idea to an established research community, but quite another to actually test out the idea on patients within the constraints of a clinical trial,” Newton said. “Of course, we hope the idea proves to be useful.”