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Oncogenic signaling in uveal melanoma

John J Park1,2, Russell J Diefenbach1,2, Anthony M Joshua2,3

  • 1Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South Wales, Australia.

Pigment Cell & Melanoma Research
|May 9, 2018
PubMed

Insights

Metastatic uveal melanoma has a poor prognosis. Early genetic mutations activate G protein-coupled receptor signaling, offering potential therapeutic targets for this eye cancer.

Area of Science:

  • Oncology
  • Ophthalmology
  • Molecular Biology

Background:

  • Uveal melanoma is the most common primary eye cancer.
  • Prognosis for metastatic uveal melanoma remains poor, with unchanged mortality rates for over 35 years.
  • Despite molecular insights, effective treatments for metastatic disease are lacking.

Purpose of the Study:

  • To review the complex interactions between genetic, molecular signaling, and prognostic profiles in uveal melanoma.
  • To discuss the clinical implications of these interactions.
  • To highlight the latest potential targets for rational therapy.

Main Methods:

  • Review of current literature on uveal melanoma genetics and molecular signaling.
  • Analysis of genetic events, including mutations in GNAQ, GNA11, CYSLTR2, PLCB4, BAP1, SRSF2/SF3B1, and EIF1AX.
  • Examination of cytogenetic changes such as chromosome 3 monosomy.

Main Results:

  • Nearly all uveal tumors exhibit early genetic events activating G protein-coupled receptor signaling via specific gene mutations.
  • Downstream signaling cascades, including protein kinase C and mitogen-activated protein kinase, are actionable targets.
  • Additional genetic alterations (BAP1, splicing factors, EIF1AX) and cytogenetic changes (chromosome 3 monosomy) influence metastatic risk.

Conclusions:

  • Understanding the interplay between genetic mutations and signaling pathways is crucial for uveal melanoma treatment.
  • Targeting activated signaling cascades and considering genetic modifiers holds promise for improving patient outcomes.
  • Ongoing clinical trials are exploring novel therapeutic strategies based on these molecular insights.
Keywords:
BAP1G protein-coupled receptorGNAQ/GNA11mitogen-activated protein kinaseuveal melanoma

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