Glutaminase Inhibitor CB-839 Enhances Proteasome Inhibitor Sensitivity in Multiple Myeloma Cells
نویسندگان
چکیده
منابع مشابه
Glutaminase inhibitor CB-839 synergizes with carfilzomib in resistant multiple myeloma cells
Curative responses in the treatment of multiple myeloma (MM) are limited by the emergence of therapeutic resistance. To address this problem, we set out to identify druggable mechanisms that convey resistance to proteasome inhibitors (PIs; e.g., bortezomib), which are cornerstone agents in the treatment of MM. In isogenic pairs of PI sensitive and resistant cells, we observed stark differences ...
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Increased nuclear factor kappaB (NF-kappaB) activity is associated with increased tumor cell survival in multiple myeloma. The function of NF-kappaB is inhibited through binding to its inhibitor, IkappaB. Release of activated NF-kappaB follows proteasome-mediated degradation of IkappaB resulting from phosphorylation of the inhibitor and, finally, conjugation with ubiquitin. We report that myelo...
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Glutamine serves as an important source of energy and building blocks for many tumor cells. The first step in glutamine utilization is its conversion to glutamate by the mitochondrial enzyme glutaminase. CB-839 is a potent, selective, and orally bioavailable inhibitor of both splice variants of glutaminase (KGA and GAC). CB-839 had antiproliferative activity in a triple-negative breast cancer (...
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Multiple myeloma remains incurable despite available therapies, and novel therapies that target both tumor cell and bone marrow microenvironment are urgently needed. Preclinical in vitro and in vivo studies show remarkable anti-multiple myeloma activity of the proteasome inhibitor bortezomib/PS-341 even in multiple myeloma cells refractory to multiple prior therapies, including dexamethasone, m...
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The proteasome has become an important target for cancer therapy with the approval of bortezomib for the treatment of relapsed/refractory multiple myeloma (MM). However, numerous patients with MM do not respond to bortezomib and those responding initially often acquire resistance. Recent clinical studies have also demonstrated that bortezomib is also inefficacious in the treatment of other type...
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ژورنال
عنوان ژورنال: Blood
سال: 2016
ISSN: 0006-4971,1528-0020
DOI: 10.1182/blood.v128.22.3294.3294