xl 184 导致了 12个结肠体外移植癌 全部缩小，其中 8个 实现稳定
XL-184（Cabozantinib）进入12/12的大肠癌植这本小说的c-Met和VEGFR2抑制剂，XL-184（Cabozantinib），导致了肿瘤生长出12 12结直肠癌（CRC）患者来源的外植体显著下降，与参展病情稳定的外植体8。该临床前研究的结果发表在AACR年会2013。
“随着分子靶向药物，我们通常会看到3个或4个CRC植模型中肿瘤的生长显著下降。在这里，我们有一种药物，是活跃在我们测试的每一个外植体，这真是令人兴奋，说：”约翰Arcaroli，博士，研究员在美国科罗拉多大学癌症中心助理教授司肿瘤内科医学院，这项研究的资深作者美国科罗拉多学院的大学。Arcaroli博士与威尔斯梅瑟史密斯博士共同领导的CU癌症中心发展治疗方案的开发和测试新化合物的胃肠道恶性肿瘤的治疗。
这种药物似乎通过抑制血管生成的工作 - 的肿瘤组织中需要的养分供给自己的新血管的生长。不同于靶向血管生成，XL-184靶血管生成不仅主驾驶员等药物的VEGFR2信号转导通路，但也可针对c-Met的一个途径是为肿瘤细胞的存活非常重要。
“其他的研究已经表明，抗VEGF治疗减少血管生成，而且还促进了肿瘤细胞的存活和转移是依赖于c-Met的信号传导途径，“Arcaroli说。“这种药物可抑制-形成血管和主逃逸机制，使肿瘤细胞。生存这两个目标的方法可能是我们所看到的这个剂非常有效的效果的原因。“
该集团还包括来自加州大学旧金山分校海伦·迪勒家庭综合癌症中心和哈佛医学院的成员，现在在研究了该化合物降低了机制肿瘤的生长。该集团还计划，以确定敏感性或耐药的预测指标到XL-184的附加 植的测试。在组合中，这项工作将有可能导致治疗转移性结直肠癌的II期生物标记物驱动的临床药物试验。
http://medicalxpress.com/news/2013-04-xl-cabozantinib-for-colorectal-cancer.html
The novel c-MET and VEGFR2 inhibitor, XL-184 (Cabozantinib), resulted in a significant decrease in tumor growth in 12 out of 12 colorectal cancer (CRC) patient-derived explants, with 8 of the explants exhibiting stable disease. The results of this preclinical work are presented at the AACR Annual Meeting 2013.
"With molecularly targeted agents, we typically see 3 or 4 CRC explant models with a significant decrease in tumor growth. Here we have a drug that was active in every explant we tested. It's really exciting," says John Arcaroli, PhD, investigator at the University of Colorado Cancer Center and assistant professor in the Division of Medical Oncology at the University of Colorado School of Medicine, the study's senior author. Dr. Arcaroli works with Wells Messersmith, MD, co-leader of the CU Cancer Center Developmental Therapeutics Program to develop and test novel compounds for the treatment of gastrointestinal malignancies.
This drug appears to work by inhibiting angiogenesis – the growth of new blood vessels that tumor tissues need to supply themselves with nutrients. Unlike other drugs that target angiogenesis, XL-184 targets not only the primary driver of angiogenesis, the VEGFR2 signaling pathway, but also targets c-Met, a pathway that is important for survival of tumor cells.
"Other studies have shown that anti-VEGF therapy decreases angiogenesis, but also promotes tumor cell survival and metastasis that is dependent on the c-MET signaling pathway," Arcaroli says. "This drug inhibits both – the formation of blood vessels and a primary escape mechanism whereby tumor cells survive. This two-target approach may be the reason we're seeing very potent effects with this agent."
The group, which also includes members from the University of California, San Francisco Helen Diller Family Comprehensive Cancer Center and from Harvard Medical School, is now investigating the mechanisms by which the compound reduces tumor growth. The group also plans additional explant testing in order to identify predictive biomarkers of sensitivity or resistance to XL-184. In combination, this work will likely lead to a Phase II biomarker-driven clinical trial of the drug in patients with metastatic colorectal cancer.
xl 184 导致了 12个结肠体外移植癌 全部缩小，其中 8个 实现稳定
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