ibrutinib + bortezomib

Ibrutinib + bortezomib is a combination of two small molecule drugs—ibrutinib, an oral irreversible inhibitor of Bruton's tyrosine kinase (BTK), and bortezomib, a reversible inhibitor of the 26S proteasome. This regimen has been investigated primarily in relapsed or refractory hematologic malignancies, including mantle cell lymphoma and multiple myeloma. The combination is designed to target distinct but complementary pathways: ibrutinib disrupts B-cell receptor signaling via BTK inhibition, impeding survival and proliferation signals in malignant B-cells; bortezomib disrupts the ubiquitin-proteasome pathway, leading to accumulation of pro-apoptotic proteins and cell-cycle arrest. Clinical studies, including phase 1/2 trials, have demonstrated activity in heavily pretreated patient populations and those with high-risk disease features, and preclinical synergy has been observed due to effects on NF-κB and related survival pathways[1][3][4][8].