bortezomib + fludarabine

Bortezomib + fludarabine is an experimental combination regimen of the small molecule proteasome inhibitor bortezomib and the purine analog fludarabine. Bortezomib reversibly inhibits the 26S proteasome, leading to accumulation of proteins involved in cell cycle regulation and apoptosis, particularly effective in cancer cells[7]. Fludarabine inhibits DNA polymerase, ribonucleotide reductase, and DNA primase, disrupting DNA synthesis and function. The combination is studied primarily in relapsed or refractory hematologic malignancies, such as non-Hodgkin’s lymphoma (NHL), mantle cell lymphoma (MCL), and chronic lymphocytic leukemia (CLL)[2][3][5]. Mechanistically, bortezomib may enhance fludarabine cytotoxicity by blocking DNA repair, increasing apoptosis, and downregulating survival pathways like NF-kB[3]. Clinical trials show the regimen is feasible, with myelosuppression and neuropathy being dose-limiting toxicities[2][3][5]. The combination does not have a unique brand name or marketing approval and is largely investigational or used in clinical trial settings.