Platelet-derived growth factor receptor (PDGFR): a target for anticancer therapeutics.
Platelet-derived growth factors (PDGFs) and their tyrosine kinase receptors (PDGFRs) have been implicated in the pathogenesis of a number of tumor types and play an important role in angiogenesis. Tumor growth can be promoted by PDGF via autocrine stimulation of malignant cells, by overexpression or overactivation of PDGFRs, or by stimulation of angiogenesis within the tumor. These mechanisms could provide possible therapeutic targets. PDGFR blockade may also lower the interstitial fluid pressure within solid tumors and enhance drug delivery. Here we discuss the possible therapeutic roles of PDGFR antagonists in the treatment of cancer, alone and in combination with chemotherapy or other targeted agents. Extensive experimental data highlight the potential therapeutic advantage of targeting PDGFR. However, recent clinical data suggest that antagonism of this growth factor is associated with fluid accumulation that could obscure any clinical benefit. Further clinical research is required to optimise inhibition of this cytokine-receptor system.
Board
Ruth
R
Cancer Research UK Department Medical Oncology, Christie Hospital, Manchester M20 4BX, UK. Ruth.Board@christie-tr.nwest.nhs.uk
Jayson
Gordon C
GC
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D018223:Dermatofibrosarcoma / Q000188:drug therapy / Q000209:etiology; D005260:Female; D005910:Glioma / Q000188:drug therapy / Q000209:etiology; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000188:drug therapy*; D009389:Neovascularization, Pathologic / Q000209:etiology* / Q000517:prevention & control; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000209:etiology; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000209:etiology; D017479:Receptors, Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors* / Q000502:physiology
D020533:Angiogenesis Inhibitors; D017479:Receptors, Platelet-Derived Growth Factor