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Efficacy of sunitinib in the treatment of metastatic uveal melanoma
Author(s) -
JMOR F,
COUPLAND SE,
DAMATO BE,
KALIRAI H
Publication year - 2010
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2010.4266.x
Subject(s) - sunitinib , medicine , receptor tyrosine kinase , cancer research , metastasis , melanoma , tyrosine kinase inhibitor , apoptosis , angiogenesis , oncology , receptor , cancer , biology , biochemistry
Purpose Almost 50% of uveal melanoma (UM) patients develop metastatic disease, despite successful treatment of the primary tumour. There is currently little in the way of therapeutic options for metastases, which are invariably fatal. Thus, there is interest in adjuvant treatments for high‐risk UM patients to treat micro‐ rather than macro‐metastatic disease. Sunitinib is a small molecule inhibitor of multiple receptor tyrosine kinases (RTKs) (VEGFR, PDGFR, C‐KIT, and RET), which play major roles in angiogenesis, tumour growth, and metastasis. Methods In this study we used 4 UM cell lines to (1) examine the expression of sunitinib target RTKs by RT‐PCR and immunofluorescence and (2) determine the effects of sunitinib alone or in combination with cisplatin, on proliferation and apoptosis. Results C‐KIT was expressed in the Mel270 and 92.1 (primary tumour) but not the Omm2.3 or Omm2.5 (metastatic lesion) cell lines. PDGFRα/β were expressed in differing cell numbers across all cell lines. VEGFR2 was expressed in Mel270’s only. VEGFR1 and RET were not expressed in any of the cell lines. A single bolus of Sunitinib (0‐1µM) reduced overall cell number in a dose dependent manner compared with untreated cells in all 4 cell lines. This was not due to a significant increase in apoptotic cell death. Furthermore, by day 7 following treatment with sunitinib ≤0.5µM, cell numbers had recovered almost to control values. This recovery was significantly reduced when an IC50 dose of sunitinib was used in combination with cisplatin (0‐1µg/ml) for each cell line. Conclusion In conclusion, these data demonstrate that a combined therapy of sunitinib and cisplatin can effectively reduce uveal melanoma cell number in vitro.