NCI Provocative Question

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Darwin, Cancer And Provocative Questions

As a young man, Charles Darwin, the British naturalist who formulated the concept of “natural selection” as a driver of evolution, observed wide variation in the species of animals on the Galapagos Islands. Cancer was not likely on his mind.

But young Darwin was confounded by, and later explained, variation in nature by “natural selection.” He postulated that nature selects certain physical attributes to pass onto offspring to better “fit” the organism, or adapt it, to the environment.

These same evolutionary principles of natural selection can be applied to manage cancer, say Moffitt researchers, who recently received a four-year, $2.1-million grant from the National Cancer Institute (NCI). Their task is to carry out research that will examine cancer’s evolutionary mechanisms of drug resistance in order to find ways to prevent it.

“Understanding cancer starts with identifying crucial environmental forces and corresponding adaptive cellular strategies,” says Robert A. Gatenby, M.D., chair of the Department of Integrated Mathematical Oncology and chair of the Department of Diagnostic Imaging. “Cancer is driven by environmental selection forces – not unlike those in the natural environment – that interact with individual cellular adaptive strategies.”

In other words, under the “selective pressure” of chemotherapy, resistant cancer cell populations will, invariably, evolve.

While targeted therapies have been among the most recent approaches to treating cancer, the evolutionary capacity of cancer populations characteristically allows rapid adaptation so that the tumor typically becomes resistant and then progresses.

“The emergence of resistance is predictable and inevitable as a fundamental property of carcinogenesis,” says Dr. Gatenby. “However, cancer cells, like any evolving population, can adapt only to current and local selection forces. They can never anticipate future selection forces. This is important, because we can understand evolutionary dynamics. So our ability to plan ahead and use evolutionary principles gives us a critical advantage in delaying or even preventing growth of resistant cancer cells. ”

Dr. Gatenby and his colleagues think that scientists should use their understanding of evolution to direct natural selection toward preventing the outgrowth of resistant cancer cells.

This line of thinking led them to receive the grant through NCI’s “Provocative Questions” project, by which researchers across the nation were asked to respond competitively to 24 provocative questions. The program was created with the hope that asking provocative questions would stimulate NCI’s research communities.

According to the NCI, its 24 provocative questions were built on: (1) specific advances in understanding cancer and cancer control, (2) broad issues on the biology of cancer, (3) the likelihoo
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