Scientists have discovered a new approach to cancer treatment which incorporates nanotechnology to deliver a one-two punch to chemotherapy-resistant cells.
Drug resistance has become the number one cause of mortality in cancer patients, where chemotherapy treatments fail to eliminate all of a patient’s cancer cells and relapse occurs. Even when doctors apply a combination of two types of cancer-fighting drugs the results are not always positive, since both drugs are not able to hit the same cancer cell at once.
Or at least until now.
Using a process known as supramolecular chemistry, researchers at Harvard Medical School and the University of Waterloo in Waterloo, Ontario, have come up with a model for incorporating two drugs within a single nanoparticle, ensuring that resistance doesn’t have the opportunity to develop within a given cell and thereby allowing the chemotherapy drugs to do their work in destroying any surviving cancer cells.
“We engineered nanoparticles with 2-in-1 drugs and compared their efficacy with two individual nanoparticles,” say the study’s authors. “We determined that 2-in-1 nanomedicines are critical to ensure co-delivery of the targeted agents to disrupt the origins of adaptive resistance.”
The new approach was made possible through mathematical simulations constructed by a team of applied mathematicians at the University of Waterloo. The team created algorithms which followed the development of cancer cells as they built up resistance to drugs over time and gave researchers a clear picture of how this process can be disrupted by the right combination of drugs.
The use of teamwork across scientific disciplines is being heralded as a new step in cancer studies. “Only recently have we begun to appreciate how important mathematics and physics are to understanding the biology and evolution of cancer,” said Dr. Mohammad Kohandel, study co-author and professor with the Department of Applied Mathematics at the University of Waterloo. “In fact, there is now increasing synergy between these disciplines, and we are beginning to appreciate how critical this information can be to create the right recipes to treat cancer.”
The research team’s real-time modeling of cellular development brought about another novel result on drug resistance. The common assumption has been that cancer cells which survive chemotherapy must somehow be structurally unique in comparison with the majority of cells which normally fall prey to the drugs. In the same way that mutations in bacteria cells evolve over time and create antibiotic resistance, this belief has led cancer specialist to concentrate on figuring out how drug-resistant cells are made differently from the others.
In fact, the new results show that under the right conditions, any cell has the power to develop an adaptive drug resistance, leading to a new hypothesis which focuses on the cell’s development of “drug-tolerant states.” “The classical dogma around resistance development relies on Darwinian principles, where cells with the right mutation are selected under chemotherapy pressure, resulting in relapse,” say the study’s authors. “Developing novel strategies to overcome the development of such adaptive resistance is critical in the search for a cure for cancer.”
The study was published in the nanotechnology journal ACS Nano.