期刊
CANCER TREATMENT REVIEWS
卷 36, 期 6, 页码 492-500出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.ctrv.2010.02.015
关键词
Dasatinib; SRC kinase; Solid tumors; Bone metastases; Preclinical; Phase 1 clinical trials; Phase 2 clinical trials
类别
资金
- Bristol-Myers Squibb
- NATIONAL CANCER INSTITUTE [P01CA095616] Funding Source: NIH RePORTER
SRC is a tyrosine kinase that plays a role in oncogenic, invasive and bone-metastatic processes. It has therefore been prioritized as a candidate therapeutic target in patients with solid tumors. Several SRC inhibitors are now in development, of which dasatinib has been most explored. Preclinical studies in a wide variety of solid tumor cell lines, including prostate, breast and glioma, have shown that that dasatinib acts as a cytostatic agent, inhibiting the processes of cell proliferation, invasion and metastasis. Dasatinib also inhibits the activity of osteoclasts, which have a major role in the development of metastatic bone lesions. Dasatinib has additive or synergistic activity in combination with a number of other agents, including cytotoxic agents and targeted therapies, providing a rationale for combination treatment in a clinical setting. Emerging clinical data with dasatinib support experimental observations, with preliminary phase 1 and 2 data demonstrating activity, both as a single agent and as combination therapy, in a range of solid tumors. Future clinical trials will further assess the clinical value of SRC inhibition with dasatinib. (C) 2010 Published by Elsevier Ltd.
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