3GatenbyRobert 4306Robert Gatenby, MD, chair of the Diagnostic Imaging and Integrated Mathematical Oncology departments, Moffitt Cancer Center, Tampa, Fla, (pictured, right) has questioned the usefulness of technological advances, such as those derived from genetic research, in the quest to better understand cancer.

Gatenby suggests that scientists who emphasize the genetic understanding of cancer might be looking in the wrong place for a better understanding of the disease.

His article “Perspective: Finding cancer’s first principles” appeared in the Outlook supplement in the November 22 issue of Nature.

Gatenby said it is better to look at cancer as a biological system subject to evolution rather than as a disease of the genes, a common phrase driving cancer research. “Cancer is a living biological system dependent on evolution and needs to be understood and treated as such. Understanding the principles governing living communities does not require and may even be obscured by genetics,” Gatenby said.

As laid out by Charles Darwin more than 150 years ago, evolution is the biological process by which organisms change in response to environmental factors, including stress, predators, nutritional sources, and climate change. As living biological organisms, cancer cells are subject to environmental factors, including the attempts to eliminate them through therapy.

“There is clear evidence that existing genetically targeted therapies generally produce temporary responses and that these therapies are ultimately defeated by the relentless evolution of cellular adaptation,” Gatenby says. “I wonder if genetic data are useful, or even necessary, to understand the evolutionary and ecological dynamics of cancer and cancer therapy.”

Gatenby makes the point that research has shown that cancer cells show great diversity, even in the same tumor. This heterogeneity should signal something important about the evolution of cancer cells and their characteristic differences in both distant and adjacent sites, he says.

“For a century, biologists and ecologists observed living systems and developed the principles governing biological individuals and communities without an understanding of their genetics,” he said. “This was possible because the biological dynamics of individuals and communities are governed by phenotypes, or observable characteristics, and not by genotypes, the genetic make up of organisms.”

Gatenby suggests that more research into the genetic nature of cancer may not yield the fruit of better knowledge about cancer as an organism. He concludes that an emphasis on huge, complex data sets acquired through molecular technology has caused us to neglect other avenues of investigation that might offer an opportunity to find cancer’s “first principles” in its evolutionary and ecological context where selective forces are at work.

“These principles will likely not be found until we begin to search in the right places,” concluded Gatenby.

His work is supported by a grant from the National Cancer Institute’s Physical Sciences in Oncology Consortium.  

[Source: Moffitt Cancer Center]