Analysis of protein tyrosine kinases expression in the melanoma metastases of patients treated with Imatinib Mesylate (STI571, Gleevec)

J Cutan Pathol. 2006 Apr;33(4):280-5. doi: 10.1111/j.0303-6987.2006.00432.x.


Background: Protein tyrosine kinase (PTK) inhibition has been identified as a promising strategy in the development of new selective therapies, targeting the signaling pathways in melanoma progression. Gleevec, a novel class of anti-tumor drugs, may have a potential therapeutic benefit in melanoma, which involves abnormal activation of abl, c-kit, and platelet-derived growth factor (PDGF) tyrosine kinases.

Methods: Tumor biopsies from 13 patients with metastatic melanoma were screened by immunohistochemistry for PTK [c-kit, C-abl, Abl-related gene (ARG), PDGF receptor-alpha (PDGFR-alpha) and PDGFR-beta] expression before and after being treated with Gleevec @ 400 mg bid for 2 weeks. Both, percentage of positive cells and staining intensity were evaluated.

Results: We found a statistically significant (p < 0.01) selective loss of PTK expression in the follow-up biopsy, both in intensity and number of positive cells. PDGFR-alpha and -beta had the highest level of expression reduction. One patient had a durable clinical response, and the follow-up biopsy showed negative expression for four of the PTKs, namely c-abl, ARG, PDGFR-alpha, and beta.

Conclusions: Our study reports for the first time the in vivo effect of Gleevec in the induction of apparently selective reduction of PTKs expression under anti-tyrosine kinases treatment, suggesting its potential role in melanoma treatment.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use*
  • Benzamides
  • Female
  • Follow-Up Studies
  • Humans
  • Imatinib Mesylate
  • Male
  • Melanoma / drug therapy*
  • Melanoma / enzymology*
  • Melanoma / secondary
  • Middle Aged
  • Piperazines / therapeutic use*
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Protein-Tyrosine Kinases / metabolism*
  • Proto-Oncogene Proteins c-abl / metabolism
  • Proto-Oncogene Proteins c-kit / metabolism
  • Pyrimidines / therapeutic use*
  • Receptors, Platelet-Derived Growth Factor / metabolism


  • Antineoplastic Agents
  • Benzamides
  • Piperazines
  • Pyrimidines
  • Imatinib Mesylate
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins c-kit
  • Receptors, Platelet-Derived Growth Factor
  • Proto-Oncogene Proteins c-abl