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Evaluation of oncogenic cysteinyl leukotriene receptor 2 as a therapeutic target for uveal melanoma

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Abstract

Uveal melanoma is a rare, but deadly, form of eye cancer that arises from melanocytes within the uveal tract. Although advances have emerged in treatment of the primary tumour, patients are still faced with vision loss, eye enucleation and lethal metastatic spread of the disease. Approximately 50% of uveal melanoma patients develop metastases, which occur most frequently in the liver. Metastatic patients encounter an extremely poor prognosis; as few as 8% survive beyond 2 years. Understanding of the genetic underpinnings of this fatal disease evolved in recent years with the identification of new oncogenic mutations that drive uveal melanoma pathogenesis. Despite this progress, the lack of successful therapies or a proven standard-of-care for uveal melanoma highlights the need for new targeted therapies. This review focuses on the recently identified CYSLTR2 oncogenic mutation in uveal melanoma. Here, we evaluate the current status of uveal melanoma and investigate how to better understand the role of this CYSLTR2 mutation in the disease and implications for patients harbouring this mutation.

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Notes

  1. Correct nomenclature of the cysteinyl leukotriene receptors (CysLT1 and CysLT2) as per the IUPHAR/BPS Guide to PHARMACOLOGY [94].

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Acknowledgements

We wish to thank Noel Horgan, Jens Rauch and Sean Ennis for discussions and comments on the manuscript.

Funding

Research related to some of the topics discussed in this review is funded by an Irish Research Council Employment Based Postgraduate Scholarship (EBP/2017/473). This project area has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 734907 (RISE/3D-NEONET project).

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Authors and Affiliations

  1. UCD School of Biomolecular & Biomedical Science, UCD Conway Institute, University College Dublin, Dublin, D04 V1W8, Ireland

    K. Slater, P. S. Hoo & B. N. Kennedy

  2. Genomics Medicine Ireland Limited, Cherrywood Business Park Building 4, Dublin, D18 K7W4, Ireland

    K. Slater

  3. Department of Surgery, Trinity Translational Medicine Institute, St. James’s Hospital, Trinity College Dublin, Dublin, Ireland

    P. S. Hoo & A. M. Buckley

  4. Department of Medical Oncology, Catalan Institute of Oncology – IDIBELL - CIBERONC, Barcelona, Spain

    J. M. Piulats

  5. Xenopat S.L., Barcelona, Spain

    A. Villanueva & A. Portela

  6. Program Against Cancer Therapeutic Resistance (ProCURE), Catalan Institute of Oncology (ICO), Bellvitge Institute for Biomedical Research (IDIBELL), Barcelona, Spain

    A. Villanueva

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  1. K. Slater
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  2. P. S. Hoo
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  5. A. Villanueva
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  6. A. Portela
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  7. B. N. Kennedy
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Contributions

KS was the primary author of the review. PSH and AMB contributed intellectual input. JMP, AV and AP were responsible for PDOX model development and drafted a section for the review. BNK contributed significant intellectual input, revised and edited the review. All authors reviewed the final manuscript.

Corresponding author

Correspondence to B. N. Kennedy.

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Conflict of interest

KS is an employee of Genomics Medicine Ireland. AV is the chief scientific officer and co-founder of Xenopat S.L. AP is the chief executive officer and co-founder of Xenopat S.L.

The other authors declare no competing financial interests that could be construed as a potential conflict of interest.

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Slater, K., Hoo, P.S., Buckley, A.M. et al. Evaluation of oncogenic cysteinyl leukotriene receptor 2 as a therapeutic target for uveal melanoma. Cancer Metastasis Rev 37, 335–345 (2018). https://doi.org/10.1007/s10555-018-9751-z

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