NF-κB as a Therapeutic Target in Multiple Myeloma
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Constitutive NF-κB signaling promotes survival in multiple myeloma (MM) and other cancers; however, current NF-κB-targeting strategies lack cancer cell specificity. Here, we identify the interaction between the NF-κB-regulated antiapoptotic factor GADD45β and the JNK kinase MKK7 as a therapeutic target in MM. Using a drug-discovery strategy, we developed DTP3, a D-tripeptide, which disrupts the...
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Constitutive activation of the canonical and noncanonical nuclear factor-κB (NF-κB) pathways is frequent in multiple myeloma (MM) and can compromise sensitivity to TRAIL. In this study, we demonstrate that Aurora kinases physically and functionally interact with the key regulators of canonical and noncanonical NF-κB pathways IκB kinase β (IKKβ) and IKKα to activate NF-κB in MM, and the pharmaco...
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Multiple myeloma is still an incurable hematological malignancy despite the development of high-dose chemotherapy with stem cell transplantation. However, the therapeutic approach for multiple myeloma has progressed significantly in the last decade. Novel agents such as bortezomib, thalidomide and lenalidomide have been introduced in clinics as expanded treatment options and have improved the o...
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PURPOSE NF-κB transcription factor plays a key role in the pathogenesis of multiple myeloma in the context of the bone marrow microenvironment. Both canonical and noncanonical pathways contribute to total NF-κB activity. Recent studies have shown a critical role for the noncanonical pathway: selective inhibitors of the canonical pathway present a limited activity, mutations of the noncanonical ...
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تاریخ انتشار 2002