期刊
CANCER LETTERS
卷 358, 期 2, 页码 100-106出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2014.12.039
关键词
Mechanisms of metronomic chemotherapy; Angiogenesis; Therapeutic resistance; MTDL alternative; Anti-tumor immunity
类别
资金
- ICBP NIH/NCI [U54 CA149233-01]
- Office of Science (BER), U.S. Department of Energy [DE-SC0001434]
- NIH [CA049248]
- NIH/NIGMS [R01 GM093050-01A1]
The administration of chemotherapy at reduced doses given at regular, frequent time intervals, termed 'metronomic' chemotherapy, presents an alternative to standard maximal tolerated dose (MTD) chemotherapy. The primary target of metronomic chemotherapy was originally identified as endothelial cells supporting the tumor vasculature, and not the tumor cells themselves, consistent with the emerging concept of cancer as a systemic disease involving both tumor cells and their microenvironment. While anti-angiogenesis is an important mechanism of action of metronomic chemotherapy, other mechanisms, including activation of anti-tumor immunity and a decrease in acquired therapeutic resistance, have also been identified. Here we present evidence supporting a mechanistic explanation for the improved activity of cancer chemotherapy when administered on a metronomic, rather than an MTD schedule and discuss the implications of these findings for further translation into the clinic. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
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