Ostman Arne, Heldin Carl-Henrik
Department of Pathology-Oncology, Cancer Center Karolinska, Karolinska Institutet, R8:03, SE-171 76 Stockholm, Sweden.
Adv Cancer Res. 2007;97:247-74. doi: 10.1016/S0065-230X(06)97011-0.
Signaling through platelet-derived growth factor (PDGF) receptors contributes to multiple tumor-associated processes. The recent introduction of clinically useful PDGF inhibitors have the last years validated PDGF receptors in malignant and stromal cells as relevant cancer drug targets. Mutational activation of PDGF receptor signaling in malignant cells has been described in some rare tumor types such as dermatofibrosarcoma protuberans, a subset of GISTs, and some hematologic malignancies. Furthermore, expression of PDGF receptors on pericytes is a common characteristic of solid tumors. The clinical efficacy of novel multikinase inhibitors, such as sunitinib and sorafenib, most likely involves targeting of PDGF receptor-dependent pericytes. Preclinical studies suggest that targeting of stromal PDGF receptors might also constitute a novel strategy to enhance tumor drug uptake. Finally, recent studies have implied both pro- and antimetastatic effects of PDGF receptors on malignant and stromal cells. The studies on the roles of PDGF receptors in cancer signaling are thus presently in a dynamic phase where collaborations between oncologists, pathologists, and tumor biologists are predicted to be highly productive.
通过血小板衍生生长因子（PDGF）受体发出的信号促成多种肿瘤相关过程。近年来，临床上有用的PDGF抑制剂的引入证实了恶性和基质细胞中的PDGF受体是相关的癌症药物靶点。在一些罕见的肿瘤类型中，如隆突性皮肤纤维肉瘤、一部分胃肠道间质瘤（GIST）以及一些血液系统恶性肿瘤中，已发现恶性细胞中存在PDGF受体信号的突变激活。此外，周细胞上PDGF受体的表达是实体瘤的一个共同特征。新型多激酶抑制剂（如舒尼替尼和索拉非尼）的临床疗效很可能涉及对依赖PDGF受体的周细胞的靶向作用。临床前研究表明，靶向基质PDGF受体也可能构成一种增强肿瘤药物摄取的新策略。最后，最近的研究表明PDGF受体对恶性和基质细胞既有促转移作用，也有抗转移作用。因此，目前关于PDGF受体在癌症信号传导中作用的研究正处于一个动态阶段，预计肿瘤学家、病理学家和肿瘤生物学家之间的合作将卓有成效。
