TY - JOUR
T1 - The development of PDGF receptor inhibitors for the treatment of Glioma
T2 - A review
AU - Badruddoja, Michael A.
AU - Elquza, Emad
AU - Welsh, James
AU - Cooke, Laurence
AU - Sanan, Abhay
AU - Stea, Baldassrre
AU - Mahadavan, Daruka
PY - 2010/5
Y1 - 2010/5
N2 - The platelet-derived growth factor (PDGF-A, PDGF-B, PDGF-C, PDGF-D) family is composed of homo- and hetero-dimers that are potent mitogens for a wide variety of cell types. They exert their biological effects by binding to two receptor tyrosine kinases (α- and β-PDGFR). PDGF-AA, -AB, -BB and -CC dimers bind to the α-PDGFR with high affinity, whereas PDGF-BB and -DD dimers bind to β-PDGFR. Aberrant PDGF signaling leads to increased interstitial fluid pressure, stromal cell recruitment and neo-angiogenesis in glioblastoma multiforme (GBM) due to deregulated autocrine/paracrine signaling. Therefore, targeting the PDGFR tyrosine kinase domain with small molecule tyrosine kinase inhibitors (TKIs) alone or in combination with chemotherapy may provide therapeutic benefit in GBM. Here we review PDGFR antagonists in clinical development including novel multi-targeted TKIs.
AB - The platelet-derived growth factor (PDGF-A, PDGF-B, PDGF-C, PDGF-D) family is composed of homo- and hetero-dimers that are potent mitogens for a wide variety of cell types. They exert their biological effects by binding to two receptor tyrosine kinases (α- and β-PDGFR). PDGF-AA, -AB, -BB and -CC dimers bind to the α-PDGFR with high affinity, whereas PDGF-BB and -DD dimers bind to β-PDGFR. Aberrant PDGF signaling leads to increased interstitial fluid pressure, stromal cell recruitment and neo-angiogenesis in glioblastoma multiforme (GBM) due to deregulated autocrine/paracrine signaling. Therefore, targeting the PDGFR tyrosine kinase domain with small molecule tyrosine kinase inhibitors (TKIs) alone or in combination with chemotherapy may provide therapeutic benefit in GBM. Here we review PDGFR antagonists in clinical development including novel multi-targeted TKIs.
KW - Clinical trials
KW - Glioblastoma multiforme
KW - Platelet derived growth factor receptor
KW - Tyrosine kinase inhibitors
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U2 - 10.2174/157018010790945887
DO - 10.2174/157018010790945887
M3 - Article
AN - SCOPUS:77949750959
SN - 1570-1808
VL - 7
SP - 290
EP - 299
JO - Letters in Drug Design and Discovery
JF - Letters in Drug Design and Discovery
IS - 4
ER -