The development of PDGF receptor inhibitors for the treatment of Glioma: A review

Michael A. Badruddoja, Emad - Elquza, James Welsh, Laurence Cooke, Abhay Sanan, Baldassarre Stea, Daruka Mahadavan

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)290-299
Number of pages10
JournalLetters in Drug Design and Discovery
Volume7
Issue number4
StatePublished - May 2010

Fingerprint

Platelet-Derived Growth Factor Receptors
Glioma
Protein-Tyrosine Kinases
Glioblastoma
Autocrine Communication
Paracrine Communication
Platelet-Derived Growth Factor
Extracellular Fluid
Receptor Protein-Tyrosine Kinases
Stromal Cells
Combination Drug Therapy
Mitogens
Therapeutics
Pressure
platelet-derived growth factor A

Keywords

  • Clinical trials
  • Glioblastoma multiforme
  • Platelet derived growth factor receptor
  • Tyrosine kinase inhibitors

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery
  • Molecular Medicine

Cite this

Badruddoja, M. A., Elquza, E. ., Welsh, J., Cooke, L., Sanan, A., Stea, B., & Mahadavan, D. (2010). The development of PDGF receptor inhibitors for the treatment of Glioma: A review. Letters in Drug Design and Discovery, 7(4), 290-299.

The development of PDGF receptor inhibitors for the treatment of Glioma : A review. / Badruddoja, Michael A.; Elquza, Emad -; Welsh, James; Cooke, Laurence; Sanan, Abhay; Stea, Baldassarre; Mahadavan, Daruka.

In: Letters in Drug Design and Discovery, Vol. 7, No. 4, 05.2010, p. 290-299.

Research output: Contribution to journalArticle

Badruddoja, MA, Elquza, E, Welsh, J, Cooke, L, Sanan, A, Stea, B & Mahadavan, D 2010, 'The development of PDGF receptor inhibitors for the treatment of Glioma: A review', Letters in Drug Design and Discovery, vol. 7, no. 4, pp. 290-299.
Badruddoja, Michael A. ; Elquza, Emad - ; Welsh, James ; Cooke, Laurence ; Sanan, Abhay ; Stea, Baldassarre ; Mahadavan, Daruka. / The development of PDGF receptor inhibitors for the treatment of Glioma : A review. In: Letters in Drug Design and Discovery. 2010 ; Vol. 7, No. 4. pp. 290-299.
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