Pérol Maurice, Arpin Dominique
Service de Pneumologie, Hôpital de la Croix-Rousse, 69317 Lyon Cedex 04.
Bull Cancer. 2007 Jul;94 Spec No:S220-31.
Inhibition of specific processes essential for tumour vascular development is actually one of the key strategies for treatment of lung cancer, for which angiogenesis is consistently predictive of a poor prognosis. The most promising agents target the vascular endothelial growth factor (VEGF) pathway, either by preventing VEGF-receptor binding as bevacizumab or inhibiting downstream receptor signaling in endothelial cells. Combination of bevacizumab with standard first-line chemotherapy in non-small cell lung cancer demonstrates a significant survival advantage comparing to chemotherapy alone, which provides the "proof of concept" for inhibition of angiogenesis in lung cancer. Development of small molecules inhibiting tyrosine kinase activity of VEGF-receptors is ongoing; many of them showed a single-agent activity but their most likely use will be in combination with chemotherapy or biological agents. Toxicity issues are of concern with the occurrence of fatal pulmonary hemorrhage after cavitation and necrosis of primary tumour, which requires appropriate selection of patients before treatment. A better understanding of the complex process of angiogenesis and of surrogate markers of treatment effect will improve our ability to design more effective therapies.
抑制肿瘤血管发育所必需的特定过程实际上是肺癌治疗的关键策略之一,对于肺癌而言,血管生成一直预示着预后不良。最有前景的药物靶向血管内皮生长因子(VEGF)通路,要么像贝伐单抗那样阻止VEGF受体结合,要么抑制内皮细胞中的下游受体信号传导。在非小细胞肺癌中,将贝伐单抗与标准一线化疗联合使用,与单纯化疗相比,显示出显著的生存优势,这为抑制肺癌血管生成提供了“概念验证”。抑制VEGF受体酪氨酸激酶活性的小分子药物正在研发中;其中许多药物显示出单药活性,但它们最可能的用途将是与化疗或生物制剂联合使用。毒性问题令人担忧,因为原发性肿瘤出现空洞和坏死后会发生致命性肺出血,这就需要在治疗前对患者进行适当筛选。更好地理解血管生成的复杂过程以及治疗效果的替代标志物,将提高我们设计更有效疗法的能力。