New York, NY (March 21, 2019) -- Researchers from Mount Sinai and IBM have discovered a novel clue in explaining how cancer cells with identical genomes can respond differently to the same therapy. In a Nature Communications paper published today, researchers reveal for the first time that the number of mitochondria in a cell is, in great part, associated with how the cancer responds to drug therapy.
Cancer is the second-leading cause of mortality worldwide, with approximately one in six deaths across the globe attributed to the disease. While treatments for cancer continue to improve as technology advances, researchers and clinicians have been unsuccessful in explaining the diversity of responses in cancer cells to treatments of oncological disease. In many cases, cancer cells with matching genetic makeup will respond differently to the same treatment. Mount Sinai and IBM researchers combined computational and biological methods to uncover a clue to this behavior.
Cells die when met with bacteria, malnourishment, or viruses. But also, to promote normal function, our bodies eliminate billions of cells each day--a process known as "programmed cell death" or apoptosis. Mitochondria, often referred to as the powerhouse of the cell because of their ability to produce cellular energy, can also act as a catalyst in the activation of programmed cell death, and certain anti-cancer drugs work by activating this process. This function encouraged researchers to explore the hypothesis that cancer cells with identical genetic makeup, but different quantities of mitochondria, may have varying susceptibility to death if exposed to the same drugs that promote apoptosis.
In exposing various types of cells to six concentrations of a pro-apoptotic drug and measuring the abundance of mitochondria within the surviving cells, Mount Sinai and IBM researchers discovered 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 analyze this data, researchers used a mathematical framework called DEPICTIVE (an acronym for DEtermining Parameter Influence on Cell-to-cell variability Through the Inference of Variance Explained) to quantify variability in the survival or death of cells due to mitochondrial abundance. Overall, the framework determined that the variability of mitochondria explained up to 30 percent of the varying responses to the pro-apoptotic drug.
"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 Pablo Meyer, PhD, Adjunct Assistant Professor of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, Team Leader of Translational Systems Biology at IBM Research, and co-corresponding author of the publication. "The outcomes of this study were truly multidisciplinary, and only made possible by the strong scientific collaboration established between Mount Sinai and IBM."
About the Mount Sinai Health System
The Mount Sinai Health System is New York City's largest integrated delivery system, encompassing eight hospitals, a leading medical school, and a vast network of ambulatory practices throughout the greater New York region. Mount Sinai's vision is to produce the safest care, the highest quality, the highest satisfaction, the best access and the best value of any health system in the nation. The Health System includes approximately 7,480 primary and specialty care physicians; 11 joint-venture ambulatory surgery centers; more than 410 ambulatory practices throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and 31 affiliated community health centers. The Icahn School of Medicine is one of three medical schools that have earned distinction by multiple indicators: ranked in the top 20 by U.S. News & World Report's "Best Medical Schools", aligned with a U.S. News & World Report's "Honor Roll" Hospital, No. 12 in the nation for National Institutes of Health funding, and among the top 10 most innovative research institutions as ranked by the journal Nature in its Nature Innovation Index. This reflects a special level of excellence in education, clinical practice, and research. The Mount Sinai Hospital is ranked No. 18 on U.S. News & World Report's "Honor Roll" of top U.S. hospitals; it is one of the nation's top 20 hospitals in Cardiology/Heart Surgery, Gastroenterology/GI Surgery, Geriatrics, Nephrology, and Neurology/Neurosurgery, and in the top 50 in six other specialties in the 2018-2019 "Best Hospitals" issue. Mount Sinai's Kravis Children's Hospital also is ranked nationally in five out of ten pediatric specialties by U.S. News & World Report. The New York Eye and Ear Infirmary of Mount Sinai is ranked 11th nationally for Ophthalmology and 44th for Ear, Nose, and Throat. Mount Sinai Beth Israel, Mount Sinai St. Luke's, Mount Sinai West, and South Nassau Communities Hospital are ranked regionally.
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About IBM Research
For more than seven decades, IBM Research has defined the future of information technology with more than 3,000 researchers in 12 labs located across six continents. Scientists from IBM Research have produced six Nobel Laureates, 10 U.S. National Medals of Technology, five U.S. National Medals of Science, six Turing Awards, 19 inductees in the National Academy of Sciences and 23 inductees into the National Inventors Hall of Fame. For more information about IBM Research, visit http://www.