Studies help explain resistance to BET inhibitors

So the team used these 3 transcripts to establish a “resistance index” that, they believe, may provide a first step toward developing a predictive biomarker.

The researchers said, collectively, their study reveals that leukemia cells can become resistant to BET inhibitors by rewiring the regulation of critical BRD4 target genes. This transcriptional plasticity highlights an emerging mode of drug resistance that is distinct from established resistance mechanisms such as mutations in binding pockets or drug elimination through efflux pumps.

Dr Zuber and his colleagues believe that a better understanding of these adaptation mechanisms will lead to combination therapies that will ultimately “outsmart” cancer cells.

“We now have learned that cancer cells can adapt to targeted therapies, but their repertoire of escape routes is quite limited,” Dr Zuber said. “A better understanding of the common escape routes will allow us to predict the next effective targeted therapy so that we are always one step ahead of the cancer cell.”