Cancer cells have been known to be able to adapt and develop a type of resistance to drugs, making it even more difficult to fight the spread of it by eradicating the tumor. A new study led by researchers from Brigham and Women's Hospital suggests that a combination of three drugs could potentially work to overcome cross-therapy resistance that make it harder for doctors to attack and put a stop to the spread of cancer cells.
The results of the recent study were published in the journal, Science Signaling.
"We have recently unraveled the complexities that come with the failure of chemotherapy," said Aaron Golman, PhD. He is also an instructor Medicine from Bringham's Division on BIoengineering. "The drugs sued for the treatment has also become a part of the problem. We needed to figure out where the resistance is coming from. After all, resistance is not an intrinsic property of cells."
The researchers of the study used computational modeling, experiments in vitro, as well as in vivo animal models. They also tested on human tumors to see how its metabolic processes are affected by the underlying chemotherapy drug. They wanted to measure its rate of tolerance as well as possible resistance to the strength of the drugs.
In accordance to what is popularly known as the Warburg Effect -- a widely known paradigm for tracking resistance of drug -- the researchers observed that the cancer cells took up the extra glucose in the blood putting all glycolytic pathways into what seemed like an overdrive. However, unlike the Warburg effect, the researchers were able to observe an increase in mitochondrial activity, which means there is a high level of oxygen consumption on a cellular level.
Using a mathematical model, Goldman and his team found that the treatment using three drugs administered at time-sensitive progression helped sensitized the cancer cells. Aside from the three identified drugs, combinations that are already clinically available could help fight the resistance of cancer cells to medication.
The researchers acknowledged that they have yet to identify a clear understanding of the cancer cell plasticity because these allow the cells to gain new metabolic phenotypes and make them drug-resistant. The researchers are hopeful that they could use mathematical modeling to increase regimens for possibly new cancer therapies.
"We are not just putting drugs together. Rather we are developing combinations that rationally address the potential resistance to achieve desired results," he added.
