Researchers identify more effective cancer treatment

Researchers at Mount Sinai and IBM have discovered a new clue by explaining how cancer cells with identical genomes can react differently to the same therapy. In one Nature Communications In an article published today, researchers reveal for the first time that the number of mitochondria in a cell is largely related to how cancer responds to drug treatment.

Cancer is the second leading cause of death in the world, with about one in six deaths worldwide attributed to the disease. As cancer treatments continue to improve as technology progresses, researchers and clinicians have failed to explain the diversity of cancer cell responses to oncological disease treatments. In many cases, cancer cells of corresponding genetic makeup respond differently to the same treatment. Researchers at Mount Sinai and IBM combined computer and biological methods to find an index of this behavior.

Cells die when they encounter bacteria, malnutrition or viruses. But also, to promote normal functioning, our body eliminates billions of cells every day – a process called "programmed cell death" or apoptosis. Mitochondria, often referred to as the motor of the cell because of its ability to produce cellular energy, can also play a catalytic role in the activation of programmed cell death, and some anticancer drugs work in activating this process. This function encouraged researchers to explore the hypothesis that cancer cells with identical genetic makeup but different amounts of mitochondria may be more likely to die if exposed to the same drugs that promote apoptosis.

By exposing various cell types to six concentrations of a pro-apoptotic drug and measuring the abundance of mitochondria in surviving cells, researchers at Mount Sinai and IBM found that surviving cells had a greater amount of mitochondria than untreated cells. This strongly suggests that cells with fewer mitochondria are more likely to respond to certain drug treatments.

To badyze these data, the researchers used a mathematical framework called DEPICTIVE (acronym for DEtermining Parameter Influence on cell-to-cell variability through the inference of the explained variance) to quantify the variability of survival or death. cell-induced mitochondrial abundance. Overall, the framework determined that mitochondrial variability accounted for up to 30% of variable responses to the pro-apoptotic drug.

"Improving our understanding of the relationship between mitochondrial variability and drug response could lead to more targeted cancer treatments, allowing us to find new ways to address the problem of drug resistance," said Pablo Meyer. PhD, Assistant Professor of Genetics and Genomics. Science, Icahn School of Medicine, Mount Sinai, IBM Research Systems Translational Biology Team Leader and co-author of the publication. "The results of this study were truly multidisciplinary and were made possible only by the solid scientific collaboration established between Mount Sinai and IBM."