27 March 2019
Several cancer drugs work by promoting “apoptosis,” or programmed cell death. Some cancer cells readily undergo apoptosis in response to these therapies, while others don’t. But why?
Researchers at the Mount Sinai School of Medicine teamed up with IBM to answer that question. And they found a clue in mitochondria, the elements of cells that produce energy. In short, cells with fewer mitochondria were more likely to respond to drugs that promote apoptosis.
The team started by exposing several types of cells, including leukemia and breast cancer cells, to six different doses of an apoptosis-promoting drug. Using a mathematical model developed by IBM, they then quantified how differences in cell survival changed according to the abundance of mitochondria.
They concluded that 30% of the variability in responses to pro-apoptosis drugs can be attributed to mitochondria. Even cancer cells with identical genes but different quantities of mitochondria could react differently to drug treatments, the researchers discovered. They published their findings in the journal Nature Communications.
"Enhancing our understanding of the relationship between mitochondria variability and drug response may lead to more effective targeted cancer treatments, allowing us to find new ways to tackle the problem of drug resistance," said co-author Pablo Meyer, Ph.D., team leader of Translational Systems Biology at IBM Research and an adjunct professor at Mount Sinai, in a statement.
The potential role of cancer cells’ energy centers in drug resistance have long been of interest in the oncology community. Last year, scientists at the University of Cincinnati discovered that genetic abnormalities in mitochondria can influence “autophagy,” the process by which cells recycle components and use them as energy sources. Those abnormalities can interfere with some cancer treatments.
Other researchers are exploring a range of options for controlling mitochondria in cancer cells, including targeting an enzyme that repairs damaged mitochondrial DNA and inhibiting mitochondria that are key to cell metabolism using the diabetes drug metformin.
The Mount Sinai and IBM researchers believe their findings will have broad utility in cancer research going forward.
“For example, high mitochondria abundance can be a non-genetic mechanism of resistance to pro-apoptotic therapeutics. Incorporation of such knowledge may be an important consideration in developing therapeutic strategies, such as combination therapies,” they wrote in the study.Print
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