Biology of advanced uveal melanoma and next steps for clinical therapeutics |
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| Authors: | Jason J Luke Pierre L Triozzi Kyle C McKenna Erwin G Van Meir Jeffrey E Gershenwald Boris C Bastian J Silvio Gutkind Anne M Bowcock Howard Z Streicher Poulam M Patel Takami Sato Jeffery A Sossman Mario Sznol Jack Welch Magdalena Thurin Sara Selig Keith T Flaherty Richard D Carvajal |
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| Institution: | 1. Dana‐Farber Cancer Institute, Harvard Medical School, Boston, MA, USA;2. Wake Forest University Cancer Center, Medical Center Boulevard, Winston‐Salem, NC, USA;3. University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA;4. School of Medicine, The Winship Cancer Institute of Emory University, Atlanta, GA, USA;5. University of Texas MD Anderson Cancer Center, Houston, TX, USA;6. University of California San Francisco Helen Diller Comprehensive Cancer Center, San Francisco, CA, USA;7. National Institute of Dental and Craniofacial Research, Bethesda, MD, USA;8. National Heart & Lung Institute, Imperial College, London, UK;9. National Cancer Institute, Bethesda, MD, USA;10. University of Nottingham, Nottingham, UK;11. The Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA;12. Vanderbilt‐Ingram Cancer Center, Vanderbilt University, Nashville, TN, USA;13. Yale Cancer Center, Yale University, New Haven, CT, USA;14. Brigham and Woman's Hospital and the Melanoma Research Foundation, CURE OM, Washington, DC, USA;15. Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA;16. Memorial‐Sloan Kettering Cancer Center, New York, NY, USA |
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| Abstract: | Uveal melanoma is the most common intraocular malignancy although it is a rare subset of all melanomas. Uveal melanoma has distinct biology relative to cutaneous melanoma, with widely divergent patient outcomes. Patients diagnosed with a primary uveal melanoma can be stratified for risk of metastasis by cytogenetics or gene expression profiling, with approximately half of patients developing metastatic disease, predominately hepatic in location, over a 15‐yr period. Historically, no systemic therapy has been associated with a clear clinical benefit for patients with advanced disease, and median survival remains poor. Here, as a joint effort between the Melanoma Research Foundation's ocular melanoma initiative, CURE OM and the National Cancer Institute, the current understanding of the molecular and immunobiology of uveal melanoma is reviewed, and on‐going laboratory research into the disease is highlighted. Finally, recent investigations relevant to clinical management via targeted and immunotherpies are reviewed, and next steps in the development of clinical therapeutics are discussed. |
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| Keywords: | Ocular Uveal Melanoma
MEK
GNAQ
GNA11 metastasis cancer |
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