瑞典医科大学卡罗林斯卡研究所的研究人员利用模式动物老鼠进行研究，发现一种可以阻断肿瘤中血管形成从而终止肿瘤生长的方法，该研究或有助于开发新的癌症治疗药物。这项研究发表在The Journal of Experimental Medicine杂志上。
当肿瘤生长到豌豆粒大小时，癌细胞需要刺激形成新的血管，以此为肿瘤的生长提供氧气和营养物质，这一过程也称为血管再生(angiogenesis)。目前科学家已经开发了大量的血管再生抑制药物，但这些药物的效果都很有限，因此，需要开发出更有效的治疗药物。
在这项新的研究中，研究人员对血管细胞表面一种ALK1受体进行研究，当阻断老鼠肿瘤中的ALK1受体时，发现血管再生受到抑制，肿瘤停止生长。ALK1受体可由信号蛋白TGF-β蛋白激活，研究表明，TGF-β家族中两种分子——TGF-β和BMP9可相互作用，共同刺激肿瘤中血管再生。
ALK1受体途径被阻断，其中一部分是由于遗传原因，另一部分原因是因为一种命名为RAP-041的药物。研究人员认为，RAP-041可与其他血管再生抑制剂共同使用，使对血管再生的抑制效果达到最大化。（生物谷Bioon.com）
生物谷推荐原始出处：
The Journal of Experimental Medicine January 11, 2010 doi:10.1084/jem.20091309
Genetic and pharmacological targeting of activin receptor-like kinase 1 impairs tumor growth and angiogenesis
Sara I. Cunha1, Evangelia Pardali2, Midory Thorikay2, Charlotte Anderberg1, Lukas Hawinkels2, Marie-José Goumans2, Jasbir Seehra3, Carl-Henrik Heldin4, Peter ten Dijke2, and Kristian Pietras1
1 Department of Medical Biochemistry and Biophysics, Division of Matrix Biology, Karolinska Institutet, Stockholm SE-171 77, Sweden
2 Department of Molecular Cell Biology and Centre for Biomedical Genetics, Leiden University Medical Center, Leiden 2300 RC, Netherlands
3 Acceleron Pharma, Cambridge, MA 02139
4 Ludwig Institute for Cancer Research, Uppsala University, Uppsala SE-751 05, Sweden
Members of the transforming growth factor β (TGF-β) family have been genetically linked to vascular formation during embryogenesis. However, contradictory studies about the role of TGF-β and other family members with reported vascular functions, such as bone morphogenetic protein (BMP) 9, in physiological and pathological angiogenesis make the need for mechanistic studies apparent. We demonstrate, by genetic and pharmacological means, that the TGF-β and BMP9 receptor activin receptor-like kinase (ALK) 1 represents a new therapeutic target for tumor angiogenesis. Diminution of ALK1 gene dosage or systemic treatment with the ALK1-Fc fusion protein RAP-041 retarded tumor growth and progression by inhibition of angiogenesis in a transgenic mouse model of multistep tumorigenesis. Furthermore, RAP-041 significantly impaired the in vitro and in vivo angiogenic response toward vascular endothelial growth factor A and basic fibroblast growth factor. In seeking the mechanism for the observed effects, we uncovered an unexpected signaling synergy between TGF-β and BMP9, through which the combined action of the two factors augmented the endothelial cell response to angiogenic stimuli. We delineate a decisive role for signaling by TGF-β family members in tumor angiogenesis and offer mechanistic insight for the forthcoming clinical development of drugs blocking ALK1 in oncology.
