Researchers design “evolutionary trap” to thwart drug resistance

Cancers and human pathogens rapidly evolve and adapt to their surrounding environment– accumulating genetic changes and even gaining or losing entire chromosomes–to develop drug resistance. This ability to adjust to changing conditions and new therapies can turn the care of patients with these diseases into a game of whack-a-mole, as clinicians hit cells with one treatment after another only to have new drug resistant forms pop up.

Stowers researchers report scientific findings that shed new light on the evolution of drug resistance. The researchers have studied how certain cell populations evolve and evade stresses, such as exposure to drugs. Based on these new insights, the researchers have proposed a strategy called an “evolutionary trap” that is a potential approach to combat human diseases associated with drug resistance.

Stowers Investigator Rong Li, PhD, who led the study, explains that this evolutionary trap uses one stress or treatment to steer a population of cells down a single evolutionary path, and then targets a weakness of the less diverse population with another stress or treatment.

“The idea of an evolutionary trap involves training the population so that it has reduced adaptability” says Li. “You take a heterogeneous population of cells and treat it with a drug so that only one specific type of genetic variant will survive. The entire population may be good at growing under that condition, but its homogeneity becomes its Achilles’ heel. Then you target that by throwing in a second drug to drastically switch the conditions.”

Guangbo Chen, a recently graduated PhD student in Li’s lab, tested this approach in a proof-of-principle study with promising results. The strategy may potentially be applied to clinical scenarios where drug resistance is a problem, such as human fungal infections and cancers.

The new approach was reported February 12, 2015, in Cell.