求助Journal of Clinical Oncology文献1篇
【题名】：ACTB-1003: An oral kinase inhibitor targeting cancer mutations (FGFR), angiogenesis (VEGFR2, TEK), and induction of apoptosis (RSK and p70S6K).【作者】：K. Patel, A. Fattaey and A. Burd
【杂志名全称】：Journal of Clinical Oncology, 2010 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
【年, 卷(期), 起止页码】：Vol 28, No 15_suppl (May 20 Supplement), 2010: e13665
【DOI】：
【全文链接】：[url]http://meeting.ascopubs.org/cgi/content/abstract/28/15_suppl/e13665[/url]
【摘要信息】：Background: ACTB-1003 is an oral kinase inhibitor targeting cancer mutations (FGFR inhibition), angiogenesis (inhibition of VEGFR2 and Tie-2) and induces apoptosis (targeting RSK and p70S6K, downstream of PI3 kinase). The multi-activity of ACTB- 1003 translates to in vivo efficacy with dose-dependent tumor growth inhibition in a variety of histological cancers including lung, breast and colorectal.
Results: ACTB-1003 is an oral kinase inhibitor with multiple modes of action, targeting cancer mutations via FGFR inhibition FGFR1 (IC50=6 nM), angiogenesis through inhibition of VEGFR2 (2 nM), Tie-2 (4 nM), and induces apoptosis likely by targeting RSK (5 nM) and p70S6K (32 nM). ACTB-1003 is highly active with dose-dependent tumor growth inhibition in cell lines with FGFR genetic alterations - OPM2 human multiple myeloma and the murine leukemia Ba/F3-TEL-FGFR1. OPM2 cells harbor the FGFR3 t(4:14) translocation, FGFR3 K650E mutation and PTEN deletion while the Ba/F3-TEL-FGFR1 cells are driven by FGFR1 over-expression. The in vivo mechanism of action studies demonstrated inhibition of RSK and p70S6K kinases coupled to the induction of apoptosis (PARP, TUNEL) in the H460 in vivo tumors. Additionally, ACTB-1003 is shown to inhibit tumor angiogenesis evident by the inhibition of CD31 staining in tumor sections. ACTB-1003 is combinable with 5- FU or paclitaxel without diminishing the activity or increasing the toxicity of these chemotherapy agents in the HCT-116 colon tumor xenograft model.
Conclusions: ACTB-1003 is an orally active kinase inhibitor that exhibits potent, low nM activity targeting mutations via FGFR inhibition, inhibition of angiogensis and induction of apoptosis. This creates the potential for additive or synergistic antitumor efficacy that can be achieved not only within each pathway but across multiple pathways with one drug. These results support the clinical testing of ACTB-1003 in the increasing number of tumor types characterized by alterations in FGF receptors.
【求助者email】：
注：求助格式请按上面的要求逐项填写，尤其是全文链接。
求助标题请用期刊缩写。
（重要！！）为提高应助速度，最好给出文献简要摘要信息，方便大家。 meeting------------->qq
回复 沙发 的帖子
请问一下，能不能帮忙找下这篇文献呢？ [quote]原帖由 [i]ansuan2010[/i] 于 2010-9-9 21:06 发表 [url=http://www.pet2008.cn/redirect.php?goto=findpost&pid=2132199&ptid=240841][img]http://www.pet2008.cn/images/common/back.gif[/img][/url]请问一下，能不能帮忙找下这篇文献呢？ [/quote]
meeting MS只有摘要！
页:
[1]