SBI Researchers combat cancer drug resistance with novel signaling analysis

Written by: SBI Staff
Written on: Tuesday, 25 May, 2021

Drug resistance in cancer therapy is one of the grand challenges facing doctors and scientists in modern medicine. According to a study published today in Cell Reports, researchers at Systems Biology Ireland (SBI) have been working to predict and combat these resistances, developing a way to accurately identify biological network context and drug-target interactions that pertain to drug resistance.

In a paper titled “A systematic analysis of signaling reactivation and drug resistance,” the SBI researchers dispel the myths about the development of drug resistances and, through experimental validation, show ways to overcome emerging resistances. The team used a systems theory, modular response analysis (MRA) and mechanistic modeling of signaling pathways to systematically investigate and quantify the changing responses of a cell’s networks related to drug interference. 

The paper addresses the known research around targeted therapy, currently one of the most innovative and most specific ways to treat cancer. However, while targeted drugs often provide striking results initially, resistance inevitably occurs and cancer cells no longer die in response to this therapy.

Professor Boris Kholodenko, corresponding author of the study and deputy director of SBI, said of the study, “Our work systematically analyses mechanisms of the emergence of resistance to targeted therapy. We proved that feedback loops cannot fully restore signaling activity that existed before, contrary to general belief in the field. It is signaling network architecture and enzyme dimerization that result in drug resistance and we show how to mitigate that.”  

“In the paper, we analyzed how to overcome these drug resistances using a combination of different drugs to kill cancer cells,” Kholodenko said.

Ultimately, this means that the researchers found that using these new methods and studying the networks and corresponding drug resistances gives a more comprehensive understanding of how to develop new and better drug combinations. The insights demonstrated in this study could be the next vital step in overcoming drug resistance in the long term.