Researchers from the School of Medicine, Mount Sinai Hospital, and IBM have found a new clue as to why cancer cells with identical genomes respond differently to the same therapy. In an article published in Nature Communications, the researchers first told that the number of mitochondria in a cell is largely due to the way the cancer responds to drug therapy.
Cancer is the second leading cause of death in the world. Although cancer treatments continue to improve as technology advances, researchers and doctors can not explain the diversity of reactions to the treatment of cancer cells. In many cases, the cancer cells with the appropriate genetic makeup will react differently to the same treatment. The researchers combined computational and biological methods to find the key to this kind of behavior of cells.
The cells are killed when hit by bacteria or viruses. But also to ensure the normal functioning of our body every day destroys billions of cells; this process is known as "programmed cell death" or apoptosis. Mitochondria are often called "powerhouse" of the cell due to its ability to produce cellular energy, can also act as a catalyst in the activation of programmed cell death, and some anti-cancer drugs work by activating the process. This feature has prompted researchers to investigate the hypothesis that cancer cells with the same genetic make-up, but with a different number of mitochondria may have a different sensitivity when exposed to the same agents that promote apoptosis.
The researchers found that different types of cells are exposed to concentrations of six pro-apoptotic drug, measuring the number of mitochondria in the cells survived (the surviving cells were more mitochondria than in untreated cells). This suggests that the cells with fewer mitochondria are more likely to respond to certain drugs.
To analyze this data, researchers used a mathematical structure called DEPICTIVE, defining the effect of the parameters on the variability from cell to cell to quantify variability in survival or cell death depending on the amount of mitochondria. In general, because of this structure we were able to determine that the variability of mitochondrial explains 30 percent of the different responses to proapoptotic drug.
"Improving our understanding of the relationship between the number of mitochondria and drug response can lead to more effective targeted cancer treatment that will help you find new ways to address the problem of drug resistance, - says Pablo Meyer, professor of genetics and genomics, co -author of the publication -. the results of this study were interdisciplinary and have only been possible thanks to the close scientific cooperation between the Mount Sinai Hospital, and IBM ».