The researchers at the Stowers Institute for Medical Research have developed a bilateral strategy that uses the adaptive nature of an evolving cell population against it. The researchers named this innovative approach as “evolutionary trap.” The study was published in the journal Cell.
First, the method was intended to guide the cell population into one evolutionary path. This step was followed by shutting off the other openings where it might rear its ugly head. Secondly, when the cells are trapped in this way, the method positions its hammer over the single remaining target and knocks out the cell population for good. This strategy might be beneficial to not only the cancer treatments but also to other clinical scenarios like fungal infections, where drug resistance is a problem.
Scientists report that cancer can adopt multiple identities. It is a disreputably evasive disease that can accumulate mutations or even cause one to gain or lose whole chromosomes. In this way, it creates genetic variants of itself i.e. resistant to whatever drug is thrown its way. Clinicians hit cancer cells with one treatment after another only to have new drug-resistant forms pop up. This ability to evolve to transient conditions and new therapies turn the cancer care into a game of whack-a-mole.
As per the research team, evolution is the creative force that shapes living organisms. Organisms are often mistaken as a machine with a blueprint that is never going to change. However, while dealing with cancers or pathogenic organisms, scientists have faced systems that continuously adapt and change so that they are moving targets. The research team urges to develop treatments that stop them from evolving altogether.
What do the researchers do?
The research team reveals that the first and most effective change experienced by the evolving cells is gain or loss of a chromosome. It is a condition called “aneuploidy.” Under changing conditions, cells can take on new characteristics for survival by basically scrambling the dosage of the genes carried on these chromosomes.
The research team targeted this evolving nature of the cells to turn it into a weakness. They intended to train the population so that it has reduced adaptability. They took a heterogeneous population of cells and treated it with a drug. In this case, only one specific type of genetic variant survived. Afterward, they targeted the same population by throwing in a second drug to drastically switch the conditions.
The research team constructed a yeast population, mimicking the multiplicity observed in fungal pathogens or human cancers. The budding yeast was treated with high concentrations of radicicol. It is a natural antibiotic and antifungal. It kills all forms of the yeast except the ones with an extra copy of chromosome XV. Furthermore, the researchers strived for pharmaceuticals that were effective against this chromosome XV gain. They found a drug called hygromycin B.
The yeast population was treated with a combination of both the drugs. Both the drugs wiped out all of the cultures effectively.
The researchers then saw if evolutionary trap strategy could improve treatment in situations where antifungals have failed. They tested the drugs against Candida. The human pathogen Candida albicans becomes resistant to the common antifungal drug called “Fluconazole.” It acquires an extra arm of chromosome 5.
The research team screened over a thousand FDA-approved drugs for those effective against this chromosomal abnormality. They found that the drug “Pyrvinium pamoate” suppressed the fungal growth in combination with Fluconazole. Note, Pyrvinium pamoate is used to treat pediatric pinworm infections.
This study is just the beginning of the concept of an evolutionary trap. There is a vast amount of data that has to be mined for other drug pairs. Scientists are looking forward to applying this strategy to clinical treatments. They are planning to collaborate with clinicians to figure out the ways to test the deeper efficacy of the concept.