Researchers at Canada’s University of Waterloo and Harvard Medical School have developed a mathematical model that can shrink tumors and prevents resistance in aggressive cancers by activating two drugs within the same cell at the same time.
The team’s mathematical model incorporated algorithms that define the phenotypic cell state transitions of cancer cells in real-time while under attack by an anticancer agent. The simulations allowed them to define the exact molecular behavior and pathway of signals, which allow cancer cells to survive treatment over time, the Waterloo News reported.
Their research was published recently in the nanotechnology journal ACS Nano,.
The group found that the PI3K/AKT kinase, which is often over-activated in cancers, enables cells to undergo a resistance program when pressured with the cytotoxic chemotherapy known as Taxanes, which is typically used in treating aggressive breast cancers. They found that vulnerabilities to small molecule PI3K/AKT kinase inhibitors exist, and can be targeted if they are applied in the right sequence with combinations of other drugs.
“We were inspired by the mathematical understanding that a cancer cell rewires the mechanisms of resistance in a very specific order and time-sensitive manner,” Aaron Goldman, a professor at Brigham and Women’s Hospital, told the publication. “By developing a 2-in-1 nanomedicine, we could ensure the cell that was acquiring this new resistance saw the lethal drug combination, shutting down the survival program and eliminating the evidence of resistance. This approach could redefine how clinicians deliver combinations of drugs in the clinic.”
Using mouse models of aggressive breast cancer, the scientists confirmed the predictions from the mathematical model that both drugs must be deterministically delivered to the same cell.
- check out the Waterloo News article