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Targeting PDGF receptors in cancer--rationales and proof of concept clinical trials.

Publication ,  Journal Article
George, D
Published in: Adv Exp Med Biol
2003

The platelet-derived growth factors (PDGF) are a pleotrophic family of peptide growth factors that signal through cell surface, tyrosine kinase receptors (PDGFR) and stimulate various cellular functions including growth, proliferation, and differentiation. To date, PDGF expression has been demonstrated in a number of different solid tumors, from glioblastomas to prostate carcinomas. In these various tumor types, the biologic role of PDGF signaling can vary from autocrine stimulation of cancer cell growth to subtler paracrine interactions involving adjacent stroma and vasculature. The tyrosine kinase inhibitor imatinib mesylate (formerly STI571, Gleevec, Novartis Pharmaceuticals Corp, East Hanover, NJ) blocks activity of the Bcr-Abl oncoprotein and the cell surface tyrosine kinase receptor c-Kit, and as such was recently approved for several indications in the treatment on chronic myeloid leukemia and gastrointestinal stromal tumors. In both of these examples the target protein was identified by an oncogenic, activating mutation. Imatinib mesylate is also a potent inhibitor of PDGFR kinase and is currently being evaluated for the treatment of chronic myelomonocytic leukemia and glioblastoma multiforme, based upon evidence in these diseases of activating mutations in PDGFR. However, the PDGF pathway may represent a therapeutic target in other solid tumors in which it is not part of the oncogenic transformation. In order to investigate the potential biologic implications of inhibiting PDGFR in these tumor types, clinical trials that investigate both established clinical endpoints of response and benefit, as well as surrogate endpoints that describe the biologic significance of PDGF inhibition in vivo are needed.

Duke Scholars

Published In

Adv Exp Med Biol

DOI

ISSN

0065-2598

Publication Date

2003

Volume

532

Start / End Page

141 / 151

Location

United States

Related Subject Headings

  • Receptors, Platelet-Derived Growth Factor
  • Pyrimidines
  • Protein-Tyrosine Kinases
  • Prostatic Neoplasms
  • Platelet-Derived Growth Factor
  • Piperazines
  • Neovascularization, Pathologic
  • Neoplasms
  • Mutation
  • Models, Biological
 

Citation

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George, D. (2003). Targeting PDGF receptors in cancer--rationales and proof of concept clinical trials. Adv Exp Med Biol, 532, 141–151. https://doi.org/10.1007/978-1-4615-0081-0_12
George, Daniel. “Targeting PDGF receptors in cancer--rationales and proof of concept clinical trials.Adv Exp Med Biol 532 (2003): 141–51. https://doi.org/10.1007/978-1-4615-0081-0_12.
George, Daniel. “Targeting PDGF receptors in cancer--rationales and proof of concept clinical trials.Adv Exp Med Biol, vol. 532, 2003, pp. 141–51. Pubmed, doi:10.1007/978-1-4615-0081-0_12.

Published In

Adv Exp Med Biol

DOI

ISSN

0065-2598

Publication Date

2003

Volume

532

Start / End Page

141 / 151

Location

United States

Related Subject Headings

  • Receptors, Platelet-Derived Growth Factor
  • Pyrimidines
  • Protein-Tyrosine Kinases
  • Prostatic Neoplasms
  • Platelet-Derived Growth Factor
  • Piperazines
  • Neovascularization, Pathologic
  • Neoplasms
  • Mutation
  • Models, Biological