Publication in Nature Communications: Preclinical study suggests proteasome inhibitor as therapy for ibrutinib-resistant chronic lymphocytic leukemia

Drug resistance remains a major challenge in chronic lymphocytic leukemia (CLL). A study led by Martina Seiffert (German Cancer Research Center) in collaboration with Sigrid S. Skånland (Institute for Cancer Research) suggests that alterations in the proteasome activity drive resistance to the BTK inhibitor ibrutinib, and that proteasome inhibitors are effective in ibrutinib resistant or refractory CLL.
Treatment with ibrutinib can induce remissions for several years, yet development of drug resistance represents a major challenge. Mutations in BTK and the downstream protein PLCG2 are commonly detected in resistant disease, while mechanisms of resistance that are not explained by these mutations have not yet been understood.