Platelet-derived growth factor

Platelet-derived growth factor (PDGF) isoforms and PDGF receptors have important functions in the regulation of growth and survival of certain cell types during embryonal development and e.g. tissue repair in the adult. Overactivity of PDGF receptor signaling, by overexpression or mutational events, may drive tumor cell growth. In addition, pericytes of the vasculature and fibroblasts and myofibroblasts of the stroma of solid tumors express PDGF receptors, and PDGF stimulation of such cells promotes tumorigenesis. Inhibition of PDGF receptor signaling has proven to useful for the treatment of patients with certain rare tumors. Whether treatment with PDGF/PDGF receptor antagonists will be beneficial for more common malignancies is the subject for ongoing studies.

The developed inhibitors are low molecular inhibitors of the receptor kinases. Several potent inhibitors of PDGF receptor kinases have been developed, including imatinib, sunitinib, sorafenib, pazopanib and nilotinib.

Importantly, there was a marked and rapid increase in Pdgfb mRNA levels in response to thalidomide, specifically within the endothelial tip cells of the developing retina, which are actively undergoing angiogenesis.

Despite these exciting findings, thalidomide should still be used with extreme caution in humans, not only because of the drugfs potent teratogenic effects within the dose range administered in the current study but also because fairly small differences in doses seem to result in dramatic differences in vascular outcomes both in vitro and in mice4