期刊
ANNALS OF ONCOLOGY
卷 21, 期 9, 页码 1756-1764出版社
OXFORD UNIV PRESS
DOI: 10.1093/annonc/mdq009
关键词
bortezomib; chemoresistance; hematologic malignancies; nuclear factor (NF)-kappa B; proteasome
类别
资金
- Millennium Pharmaceuticals, Inc.
Background: Proteasome inhibition results in antitumor activity through various mechanisms, including disruption of cell cycle progression and control, induction of apoptosis, and inhibition of proliferation. Design: This review assesses preclinical data on the ability of bortezomib, the first proteasome inhibitor approved for clinical use, to enhance antitumor activity of other agents and to overcome chemoresistance in hematologic malignancies and discusses mechanisms by which such activity arises. Results: Bortezomib has been shown to affect multiple cellular pathways and levels of numerous intracellular proteins, including targets of importance in hematologic malignancies. These mechanisms have shown additive or synergistic effects in vitro and in vivo with those of conventional therapeutic and novel targeted agents. Additionally, targets of proteasome inhibition are implicated in resistance or lack of sensitivity to different therapies. Bortezomib in combination with other agents has been shown to overcome resistance to those agents and to resensitize cells to agents to which they were previously unresponsive. Conclusions: This review indicates the potential utility of proteasome inhibition for substantially enhancing activity of other therapeutic approaches. It explains the mechanisms responsible for the observed clinical activity of bortezomib-based regimens and elucidates novel therapeutic approaches through identification of combinations of agents with complimentary mechanisms of action.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据