PDGF receptors as cancer drug targets
PDGF receptors as cancer drug targets
复制标题
DOI：
10.1016/s1535-6108(03)00089-8
复制
发表时间：
2003-05-01
期刊：
影响因子：
50.3
通讯作者：
Östman, A
中科院分区：
文献类型：
--
作者：
Pietras, K;Sjöblom, T;Östman, A
自从20年前发现转化中的逆转录病毒V-sis癌基因来源于血小板衍生生长因子(PDGF)B链基因以来，PDGF信号通路一直是癌症治疗的有趣靶点。除了它在刺激肿瘤细胞自分泌生长方面的作用外，PDGF还被认为可以调节肿瘤间质成纤维细胞和肿瘤血管生成(图1)。临床上有用的PDGF受体拮抗剂的出现，如Glivec(STI571/Gleevec)，现在允许评估PDGF受体信号在恶性肿瘤中的重要性(Buchdunger等人，1996年；CapDeville等人，2002年)。本文综述了PDGF的生物学特性，并讨论了PDGF受体在不同肿瘤间隔区表达的作用。特别强调了两组最近的发现：第一组显示了在自分泌环境中对PDGF拮抗剂的临床反应，第二组显示了在动物模型中靶向肿瘤间质中的PDGF受体的有益效果。
Ever since the discovery 20 years ago that the transforming retroviral v-sis oncogene is derived from the platelet-derived growth factor (PDGF) B chain gene, PDGF signaling has been an interesting target for cancer treatment. In addition to its role in autocrine growth stimulation of tumor cells, PDGF has also been suggested to regulate tumor stroma fibroblasts and tumor angiogenesis (Figure 1). The occurrence of clinically useful PDGF receptor antagonists, like Glivec (STI571/Gleevec), now allows for an evaluation of the importance of PDGF receptor signaling in malignancies (Buchdunger et al, 1996; Capdeville et al., 2002). This review summarizes the biology of PDGF and discusses the role of PDGF receptor expression in different tumor compartments. Two sets of recent findings are particularly emphasized: the first set demonstrates clinical responses to PDGF antagonists in autocrine settings, and the second set presents beneficial effects of targeting PDGF receptors in the tumor stroma in animal models.