Identification of potential treatment strategies to overcome acquired bortezomib-resistance due to clonal evolution

In the present study, we have established and characterized bortezomib-resistant cell lines BR1 and BR2, and identified upregulation of proteasome pathway as the potential mechanism underlying bortezomib resistance.

Furthermore, both the cell lines retained sensitivity towards imatinib suggesting the lack of general resistance towards broad classes of inhibitors. Notably, BR1 and BR2 showed increased sensitivity than the parental cell line towards the next-generation proteasome inhibitor carfilzomib, suggesting its utility in treating patients who relapse upon bortezomib treatment. When compared to the wild type cell line, BR1 and BR2 displayed similar sensitivity towards sorafenib and vorinostat, but enhanced sensitivity towards geldanamycin treatment.