Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, Biomedical Center, Box 582, SE-75123 Uppsala, Sweden.
Department of Pharmaceutical Biosciences, Uppsala University, Biomedical Center, Box 591, SE-751 24 Uppsala, Sweden.
Mol Aspects Med. 2018 Aug;62:75-88. doi: 10.1016/j.mam.2017.11.007. Epub 2017 Nov 15.
Platelet-derived growth factors (PDGF) promotes cell proliferation, survival and migration, primarily of cells of mesenchymal origin. Dysfunction of PDGF signaling has been observed in a wide array of pathological conditions, such as cancer, fibrosis, neurological conditions and atherosclerosis. Reported abnormalities of the PDGF pathway include overexpression or amplification of PDGF receptors (PDGFRs), gain of function point mutations or activating chromosomal translocations. Current development of therapeutic drugs often aims at producing compounds that specifically target interaction between PDGFs and their receptors by specific DNA aptamers and ligand traps, or downregulate PDGFRs with blocking antibodies, or inhibit tyrosine kinase activity of PDGFRs with small molecules. In this review, we discuss some of the approaches taken to interfere with PDGF signaling, review a panel of existing therapeutic drugs, and consider clinically successful cases and remaining challenges.
血小板衍生生长因子（PDGF）主要促进间充质来源细胞的增殖、存活和迁移。PDGF 信号转导功能障碍在广泛的病理条件下观察到，如癌症、纤维化、神经状况和动脉粥样硬化。报道的 PDGF 途径异常包括 PDGF 受体（PDGFRs）的过表达或扩增、功能获得性点突变或激活染色体易位。目前治疗药物的开发通常旨在产生化合物，通过特异性 DNA 适体和配体陷阱特异性靶向 PDGFs 与其受体之间的相互作用，或用阻断抗体下调 PDGFRs，或用小分子抑制 PDGFRs 的酪氨酸激酶活性。在这篇综述中，我们讨论了一些干扰 PDGF 信号的方法，回顾了一组现有的治疗药物，并考虑了临床成功的案例和仍然存在的挑战。
