MAY 31, 2018, NEW YORK — A Ludwig Cancer Research study has uncovered an entirely novel mechanism by which cells enter a state of dormancy as tissues starved of oxygen become increasingly acidic. The study, led by Chi Van Dang, scientific director of the Ludwig Institute for Cancer Research, has potentially significant implications for cancer therapy: Large swaths of solid tumors are often deprived of oxygen, and cells in such patches are thought to be a major source of drug resistance and disease relapses.
Published today in the journal Cell, the study details how in response to acidity cells turn off a critical molecular switch known as mTORC1 that, in ordinary conditions, gauges the availability of nutrients before giving cells the green light to grow and divide. That event, Dang and his colleagues show, shuts down the cell’s production of proteins, disrupting their metabolic activity and circadian clocks, and pushing them into a quiescent state. They also demonstrate that this acid-mediated effect might be relatively easy to reverse–a finding that could help improve a variety of cancer therapies.
“In tumors grafted into mice, we see mTOR activity in spotty places where there’s oxygen,” says Dang who is also a
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