Imatinib and dasatinib inhibit hemangiosarcoma and implicate PDGFR-β and Src in tumor growth

Erin B. Dickerson, Kevin Marley, Wade Edris, Jeffrey Tyner, Vidya Schalk, Valerie MacDonald, Marc Loriaux, Brian Druker, Stuart C. Helfand

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Hemangiosarcoma, a natural model of human angiosarcoma, is an aggressive vascular tumor diagnosed commonly in dogs. The documented expression of several receptor tyrosine kinases (RTKs) by these tumors makes them attractive targets for therapeutic intervention using tyrosine kinase inhibitors (TKIs). However, we possess limited knowledge of the effects of TKIs on hemangiosarcoma as well as other soft tissue sarcomas. We report here on the use of the TKIs imatinib and dasatinib in canine hemangiosarcoma and their effects on platelet-derived growth factor receptor β (PDGFR-β) and Src inhibition. Both TKIs reduced cell viability, but dasatinib was markedly more potent in this regard, mediating cytotoxic effects orders of magnitude greater than imatinib. Dasatinib also inhibited the phosphorylation of the shared PDGFR-β target at a concentration approximately 1000 times less than that needed by imatinib and effectively blocked Src phosphorylation. Both inhibitors augmented the response to doxorubicin, suggesting that clinical responses likely will be improved using both drugs in combination; however, dasatinib was significantly (P

Original languageEnglish (US)
Pages (from-to)158-168
Number of pages11
JournalTranslational Oncology
Volume6
Issue number2
DOIs
StatePublished - Apr 2013

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Hemangiosarcoma
Protein-Tyrosine Kinases
Growth
Neoplasms
Phosphorylation
Platelet-Derived Growth Factor Receptors
Receptor Protein-Tyrosine Kinases
Drug Combinations
Sarcoma
Doxorubicin
Blood Vessels
Canidae
Cell Survival
Dogs
Imatinib Mesylate
Dasatinib
Therapeutics

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Dickerson, E. B., Marley, K., Edris, W., Tyner, J., Schalk, V., MacDonald, V., ... Helfand, S. C. (2013). Imatinib and dasatinib inhibit hemangiosarcoma and implicate PDGFR-β and Src in tumor growth. Translational Oncology, 6(2), 158-168. https://doi.org/10.1593/tlo.12307

Imatinib and dasatinib inhibit hemangiosarcoma and implicate PDGFR-β and Src in tumor growth. / Dickerson, Erin B.; Marley, Kevin; Edris, Wade; Tyner, Jeffrey; Schalk, Vidya; MacDonald, Valerie; Loriaux, Marc; Druker, Brian; Helfand, Stuart C.

In: Translational Oncology, Vol. 6, No. 2, 04.2013, p. 158-168.

Research output: Contribution to journalArticle

Dickerson, Erin B. ; Marley, Kevin ; Edris, Wade ; Tyner, Jeffrey ; Schalk, Vidya ; MacDonald, Valerie ; Loriaux, Marc ; Druker, Brian ; Helfand, Stuart C. / Imatinib and dasatinib inhibit hemangiosarcoma and implicate PDGFR-β and Src in tumor growth. In: Translational Oncology. 2013 ; Vol. 6, No. 2. pp. 158-168.
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