Understanding The Logic Of Cancer: Physicists Unravel The Rules Of Metastasis

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The team found that cancer metastasis has three states: “on,” “off,” and a partial on-off state known as a “hybrid.” Milosz1, CC BY 2.0

A new study may represent the first step towards disrupting the spread of tumors in cancer patients. At Rice University’s Center for Theoretical Biological Physics (CTBP), researchers have begun to unravel the genetic mechanisms of metastasis — the process whereby a cancer invades other parts of the body. The findings sets the stage for new treatment strategies designed to anticipate and preempt additional tumor growth.

Published in the journal Proceedings of the National Academy of Sciences, the study sought to illuminate the “logic” of cancer with the fundamental rules of physics. Specifically, the researchers wanted to understand the basic genetic “decisions” the cancer must make in order to sustain tumor growth and invade other organs. According to senior investigator Eshel Ben-Jacob, analyses suggested that the daunting complexity of metastasis can be reduced to a few rudimentary mechanisms.

"Cancer cells behave in complex ways, and this work shows how such complexity can arise from the operation of a relatively simple decision-making circuit," he said in a press release. "By stripping away the complexity and starting with first principles, we get a glimpse of the 'logic of cancer' — the driver of the disease's decision to spread."

To investigate this “logic,” the researchers studied the behavior of microRNA in other cellular decision-making circuits. In an experiment, Ben-Jacob and his team looked at the genetic circuit that allows cells decide whether to assume an epithelial state or a mesenchymal state. The specifics of the states isn't that important; what matters is the act of toggling itself. In other words, the cell is making a "decision." When mapped onto cancerous cells, this decision-making framework provided a glimpse into the rules of metastasis.

The team found that cancer cells spread in accordance with a ternary switch — in other words, by toggling between three distinct decisions. Metastasis is either “on,” “off,” or in a partial on-off state known as a “hybrid.” It is during the hybrid state that cancer metastasis use stem-cell properties to evade treatment and immune responses.

"Now that we understand what drives the cell to select between the various states, we can begin to think of new ways to outsmart cancer," Ben-Jacob explained. "We can think about coaxing the cancer to make the decision that we want, to convert itself into a state that we are ready to attack with a particularly effective treatment."

The findings will hopefully allow scientists to develop new ways of tracking and controlling the spread of cancer within the body. Such treatment strategies could save the life of countless cancer patients – particularly patients with pancreatic cancer, for whom metastasis is almost always an issue at the time of diagnosis.

Source: M. Lu, M. K. Jolly, H. Levine, J. N. Onuchic, E. Ben-Jacob.MicroRNA-based regulation of epithelial-hybrid-mesenchymal fate determinationProceedings of the National Academy of Sciences, 2013.

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