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Bortezomib + clofarabine is an investigational combination therapy consisting of two small molecule chemotherapeutic agents. Bortezomib is a proteasome inhibitor approved for multiple myeloma and mantle cell lymphoma, while clofarabine is a purine nucleoside analog approved for pediatric relapsed/refractory acute lymphoblastic leukemia. The combination has been studied in phase I clinical trials for adults with refractory solid tumors, lymphomas, or myelodysplastic syndromes. Mechanistically, bortezomib induces mitochondrial apoptosis by increasing the pro-apoptotic protein BAX and activating caspase-3; clofarabine can upregulate p53, which also activates BAX. Preclinical models suggest that this drug pair leads to higher levels of BAX and increased apoptosis compared to either agent alone[1][2][3][4].
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