Yale Daily News

A recently published Yale study explored how cancer cell plasticity — which refers to the ability of cells to adapt their phenotypes in response to environmental signals without undergoing genetic alterations — might impact the development, progression and treatment of cancer.   

Cancer remains a challenging disease to treat primarily due to its unpredictable nature and ability to evade traditional therapies. Some of the characteristics of cancer cells are uncontrolled growth, tissue invasion and metastasis, angiogenesis and resistance to apoptosis, among others. 

To analyze the resistance displayed by cancers to currently available treatments, the team explored the plastic behavior of cancer cells, aiming to understand the role of genetic and non-genetic mechanisms in cancer development. Additionally, they sought to integrate scientific knowledge about organismal development and aging into the overall understanding of cancer.

“The surprising result and the result that holds great promise is that we can describe the underlying mechanisms using mathematical approaches that have also been used in physics and chemistry,” Andre Levchenko, professor of biomedical engineering at Yale and co-author of this study, wrote to the News. “The analysis also suggests new avenues for cancer treatment and prevention.” 

The authors described the crucial role of entropy, a measure of informational uncertainty, in comprehending the intricate behavior of cancer and developing novel therapeutic targets. They highlighted how increased entropy can result in increased variability, enabling cancer cells to access hidden cellular states that may contribute to their capacity to evade detection and treatment.

Megan King, associate professor of cell biology and of molecular, cellular and developmental  biology at Yale, emphasized that epigenetic modification can instigate the acquisition of tumor cell characteristics, and therefore can be a cancer treatment target. 

“Epigenetic alterations can drive changes in cell behavior, for example such that they adopt features of tumor cells, both more quickly and also in a reversible fashion,” King told the News. “Rewiring the epigenome is therefore a strategy that tumor cells leverage in their evolution and can also be a target for cancer therapies.”

To identify cellular mechanisms that enable cancer cells to resist medical interventions  and natural immune responses, the authors explored the notion of stochastic processes — mathematical models that describe the evolution of random variables over space or time — in biological systems. According to the researchers, the concept of biological stochasticity may pave the way for more effective strategies for cancer prevention, diagnosis and treatment, as well as improved clinical outcomes.

Xavier Llor, professor of medicine at Yale and co-director of the Smilow Cancer Genetics and Prevention Program, emphasized that the process by which the environments affects cell regulation is intricate and not well understood. However, he mentioned that “the now possible study of individual cells should help understand these interactions and how malignant cells escape natural and treatment defenses.”

According to Levchenko, the team hopes that this work provides a basis for more quantitative approaches to cancer treatment and prevention, in addition to fostering additional computational and experimental work in both basic cancer and clinical applications. 

“These approaches are still in their infancy and frequently only consider a part of the problem,” Levchenko told the News. “Our approaches aim to be more comprehensive, systems level, combining multiple mechanisms into the same framework.”

The study was featured in the journal Science.