“People die when their infections or tumors become drug resistant,” said Andrew Read, Evan Pugh Professor of Biology and Entomology and Eberly Professor of Biotechnology at Penn State, and the lead author of a recent study published in PLoS Biology.1
Using mathematical analysis the researchers identified factors that would determine which of 2 treatment strategies, the containment or the elimination of an infection or tumor, would be most effective. In some situations, the containment of an infection to a tolerable level can extend the duration of time that a treatment can be effective and improve patient outcomes. In other situations quick, aggressive treatment aimed at eliminating the infection or tumor is required.
The researchers compared the containment or elimination strategies with the objective of increasing the amount of time before drug resistance develops. The treatment approach leading to the longest time before treatment failure was dependent on disease characteristics and the patient.
Two main factors determined if an infection or tumor would develop drug resistance. The first was the rate at which cells that are responsive to treatment become resistant. The second is competitive suppression, where cells that are responsive to a treatment out-compete resistant cells for resources, thereby slowing the spread of resistance.
“The standard practice has been to treat infections and tumors as aggressively as possible to minimize the risk of cells becoming resistant,” said Read, “but our analysis shows that, in many situations, containing the infection or tumor to allow for competitive suppression of resistant cells can increase the time to treatment failure.” Overall, this study provides a framework to help guide physicians in making difficult treatment decisions on case-by-case basis.
1. Hansen E, Woods RJ, Read AF. How to use a chemotherapeutic agent when resistance to it threatens the patient. PLoS Biol. 2017 Feb 9. doi: 10.1371/journal.pbio.2001110 [Epub ahead of print]