SE Valley Times

Cancer cells are driven by the same imperative guiding all living things: to grow, survive, and reproduce. Although cancer’s evolutionary underpinnings have been recognized since the 1950s, clinicians have been slow to apply the lessons of evolution to combat this deadly disease, which remains the second-leading cause of death, claiming 9.7 million lives worldwide in 2022.

Carlo Maley is a researcher in the Biodesign Center for Biocomputing, Security and Society, director of the Arizona Cancer Evolution Center, and professor with ASU’s School of Life Sciences. A new review by Arizona State University researcher Carlo Maley and Lucie Laplane from the University of Paris Pantheon-Sorbonne examines the prevailing theory of cancer evolution. The authors highlight both practical and theoretical limitations of the clonal model of cancer evolution and propose areas for improving the model’s relevance and accuracy.

The study suggests that the model could be improved by acknowledging that cancer cells inherit not only genetic mutations but also other traits that allow them to rapidly adapt to their environment — even without genetic alterations. Cancer cells are highly responsive to their surrounding environment, which can promote or suppress their growth. Further, cancer evolution often follows complex dynamics, leading to tangled and unpredictable growth patterns.

Cancer biologists have traditionally defined a "clone" as a group of cells descending from a single ancestor cell and sharing the same genetic makeup. But cancer cells mutate so fast that no two cells have the same genetic makeup. The study proposes replacing the concept of a clone with a focus on cell genealogies that record history and define structure within tumors.

The value of an effective model lies in its ability to explain how and why cancers evolve and respond to therapy. By refining the clonal evolution model, this study paves the way for more effective cancer therapies that consider the full complexity of cancer cell evolution.

The research appears in Nature Reviews Cancer.

“Evolution is such a powerful idea that when we apply it to the cells in our bodies, it explains how we get cancer and why it is so hard to cure. But like everything in the real world, it’s complicated,” Maley says. “We set out to address complications people have pointed out and show how they can be integrated into our theory of how cancer works.”

Maley's collaborator Lucie Laplane visited ASU for this research project with support from ASU's Center for Biology and Society and a grant from the McDonnell Foundation.

The clonal evolution theory suggests that cancer begins from a single cell undergoing mutations enabling faster growth than normal cells. As this cell divides, some offspring may gain additional mutations providing greater survival advantages over time leading to diverse populations driven by those most fit for survival.

To address these issues, researchers explore limits within current evolutionary theories on cancer. A key challenge involves expanding these theories beyond just genes during cell division including material exchange among cells developing better methods identifying tracking variations.

Traditionally assumed DNA largely determines behavior progression includes growth spread response treatments challenging view highlighting factors influence surrounding environment epigenetic changes chemical modifications altering gene expression without changing sequence another assumption development traced tree main ancestor branching implying neat predictable pattern however suggests not always case merging acquiring traits resembling network multiple influences paths further initially considered continuous gradual process shown occur stasis gradual change sudden punctuated bursts

The clonal evolution model has shifted perspectives on viewing dynamic nature discrediting search single "magic bullet" treatment prompting changes research approaches clinical impact limited evolutionary strategies adaptive therapy showing encouraging results dramatic improvements understanding multifaceted nature critical developing effective treatments targeting not only genetic mutations but also epigenetic changes interactions surrounding environment improving outcomes refining paving way considering full complexity