The PDGF/PDGFR pathway as a drug target

• Published in: Molecular aspects of medicine Vol. 62; pp. 75 - 88
• Main Authors: Papadopoulos, Natalia, Lennartsson, Johan
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.08.2018
• Subjects: Animals; Cell Movement; Cell Proliferation; Cell Survival; Drug targeting; Genetic Variation; Humans; Molecular Targeted Therapy; PDGF pathway; PDGFR; Platelet-Derived Growth Factor - genetics; Platelet-Derived Growth Factor - metabolism; Protein Kinase Inhibitors - pharmacology; Receptors, Platelet-Derived Growth Factor - genetics; Receptors, Platelet-Derived Growth Factor - metabolism; Signal Transduction - drug effects; Therapeutics; CSF1R; GIST; BBB; RNA; FLT3; VEGF; MS; ALS; PDGF pathway; FGFR; ECM; TKI; GBM; PD; PDGF; DNA; Therapeutics; TK; Kit; PDGFR; Drug targeting; ATP
• ISSN: 0098-2997; 1872-9452; 1872-9452
• DOI: 10.1016/j.mam.2017.11.007

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.