Cancer Research Institute, M.D. Anderson Cancer Center Orlando, 110 Bonnie Loch Ct., Mail Point 47, Orlando, FL 32806, USA.
Int J Oncol. 2010 Jan;36(1):5-18.
The therapeutic potential of targeting tumor endothelium and vascular supply is now widely recognized to treat different diseases. One such disease is cancer; where endothelial cells are actively proliferating to support the tumor growth. Solid tumors cannot grow beyond the size of a few millimeters without inducing the proliferation of endothelium and formation of new blood vessels. Hence it is crucial to search for new agents that selectively block tumor blood supply. These include anti-angiogenic molecules, vascular disrupting agents or endothelial disrupting agents. The anti-angiogenic molecules such as monoclonal antibodies and tyrosine kinase inhibitors disrupt endothelial cell survival mechanisms and new blood vessel formation, and vascular disrupting agents for instance ligand-directed and small molecules can be used to disrupt the already existing abnormal vasculature that support tumors by targeting their dysmorphic endothelial cells. The recent advances in this area of research have identified a variety of investigational agents which are currently in clinical development at various stages and some of these candidates are already approved in cancer treatment. This report will review some of the recent developments and most significant advances in this field and outline future challenges and directions.
靶向肿瘤内皮细胞和血管供应的治疗潜力现已被广泛认可,可用于治疗不同疾病。癌症就是其中一种疾病;在此类疾病中,内皮细胞会积极增殖,以支持肿瘤生长。如果没有内皮细胞的增殖和新血管的形成,实体瘤的生长大小将无法超过几毫米。因此,寻找选择性阻断肿瘤血液供应的新药物至关重要。这些药物包括抗血管生成分子、血管破坏剂或内皮破坏剂。抗血管生成分子,如单克隆抗体和酪氨酸激酶抑制剂,可破坏内皮细胞的存活机制和新血管的形成,而血管破坏剂,例如配体导向和小分子药物,可以通过靶向其畸形内皮细胞来破坏支持肿瘤的已存在的异常血管系统。这一研究领域的最新进展已经确定了多种目前处于不同临床开发阶段的研究性药物,其中一些候选药物已在癌症治疗中得到批准。本报告将综述该领域的一些最新进展和重要进展,并概述未来的挑战和方向。