Harvard Medical School, Pediatric Medical Neuro-Oncology, Dana-Farber Cancer Institute and Children's Hospital of Boston, Boston, MA 02115, USA.
Expert Opin Investig Drugs. 2009 Jul;18(7):973-83. doi: 10.1517/13543780903025752.
Significant advances in the diagnosis and treatment of brain tumors have been made through better imaging, surgical techniques and advances in radiation therapy. However, the cure rate for most adult and pediatric brain tumor patients has not mirrored this success. Angiogenesis, the development of neovascularization, provides the required nutrients and oxygen to an expanding tumor and is controlled by a complex balance of proangiogenic cytokines and antiangiogenic factors. A series of new inhibitors of angiogenesis are now in clinical trials. Most of these rely on inhibiting tumor cell-mediated cytokines or blocking the activation of their cognate receptors. Cytotoxic chemotherapy, by contrast, targets dividing cells but can be modulated to attack dividing endothelial cells. This review will focus on the use of low-dose antiangiogenic (also called metronomic) chemotherapy to inhibit endothelial cell function and resultant neovascularization in the treatment of adult and pediatric brain tumors. By examining the biology and preclinical findings that led to the development of antiangiogenic/metronomic chemotherapy, clinical studies have been undertaken that support the role of this approach in the clinic, and have led to the introduction of a number of markers being used to better predict active combinations and appropriate patient populations.
通过更好的成像、手术技术和放射治疗的进步，脑肿瘤的诊断和治疗取得了重大进展。然而，大多数成人和儿童脑肿瘤患者的治愈率并没有反映出这一成功。血管生成，即新血管的形成，为不断扩大的肿瘤提供所需的营养和氧气，由促血管生成细胞因子和抗血管生成因子的复杂平衡控制。一系列新的血管生成抑制剂目前正在临床试验中。这些抑制剂大多依赖于抑制肿瘤细胞介导的细胞因子或阻断其同源受体的激活。相比之下，细胞毒性化疗针对分裂细胞，但可以调节以攻击分裂的内皮细胞。这篇综述将重点介绍低剂量抗血管生成（也称为节拍）化疗在治疗成人和儿童脑肿瘤中抑制内皮细胞功能和由此产生的新血管生成的作用。通过检查导致抗血管生成/节拍化疗发展的生物学和临床前发现，已经开展了一些临床研究，支持这种方法在临床上的作用，并导致引入了一些标志物，以更好地预测有效的组合和合适的患者群体。
