Combined PKC and MEK inhibition for treating metastatic uveal melanoma

M. S. Sagoo, J. William Harbour, J. Stebbing, A. M. Bowcock

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Uveal melanoma (UM) is the most common primary intraocular malignancy and the second most common form of melanoma. UM has a strong tendency for metastatic disease, and no effective treatments have yet been identified. Activating oncogenic mutations are commonly found in GNAQ and GNA11 in UM, and inhibiting key downstream effectors of the GNAQ/11 signaling pathway represents a rational therapeutic approach for treating metastatic UM. Chen et al., doi:10.1038/onc.2013.418, now confirm activation of the MAPK and PKC pathways as a result of GNAQ and GNA11 activating mutations in melanocytes, and they demonstrate that MAPK activation occurs downstream of PKC activation. PKC inhibitors disrupt MAPK signaling and block proliferation of GNAQ/11 mutant UM cell lines and slow the in vivo growth of xenografted UM tumors without inducing their shrinkage. However, a combination of PKC and MEK inhibition led to sustained MAPK pathway inhibition and tumor regression in vivo. Hence, the authors concluded that MEK and PKC inhibition is synergistic, with superior efficacy to treatment of GNAQ/GNA11 mutant UMs with either drug alone.

Original languageEnglish (US)
Pages (from-to)4722-4723
Number of pages2
JournalOncogene
Volume33
Issue number39
DOIs
StatePublished - Sep 1 2014

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Mitogen-Activated Protein Kinase Kinases
Mutation
Second Primary Neoplasms
Melanocytes
Uveal melanoma
Melanoma
Neoplasms
Cell Line
Growth
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics
  • Medicine(all)

Cite this

Combined PKC and MEK inhibition for treating metastatic uveal melanoma. / Sagoo, M. S.; William Harbour, J.; Stebbing, J.; Bowcock, A. M.

In: Oncogene, Vol. 33, No. 39, 01.09.2014, p. 4722-4723.

Research output: Contribution to journalArticle

Sagoo, M. S. ; William Harbour, J. ; Stebbing, J. ; Bowcock, A. M. / Combined PKC and MEK inhibition for treating metastatic uveal melanoma. In: Oncogene. 2014 ; Vol. 33, No. 39. pp. 4722-4723.
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