PDGFs and their cognate
tyrosine kinase alpha- and beta-receptors are involved in multiple
tumor-associated processes including autocrine growth stimulation of
tumor cells, stimulation of
tumor angiogenesis and recruitment and regulation of
tumor fibroblasts. The recent development of clinically useful PDGF antagonists, like
STI571/
Glivec, has increased the interest in
PDGF receptors as
cancer drug targets. Autocrine
PDGF receptor signaling occurs in certain
malignancies characterized by mutational activation of PDGF or
PDGF receptors, for instance, dermatofibrosaracoma protuberans,
gastrointestinal stromal tumors, and
hypereosinophilic syndrome. The roles of PDGF in regulation of
tumor angiogenesis and
tumor fibroblasts are more general, and probably occur in most common solid
tumors. Concerning
tumor angiogenesis recent studies have predominantly focused on the importance of
PDGF receptor signaling for
tumor pericyte recruitment.
PDGF receptors in the
tumor stroma have also attracted attention as interesting
drug targets because of their function as regulators of
tumor interstitial fluid pressure,
tumor transvascular transport and
tumor drug uptake. In summary, the improved understanding of the role of PDGF signaling in
tumor biology, and the introduction of PDGF antagonists, has set the stage for a continued development of PDGF antagonists as novel
cancer drugs.