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Updated: Mar 7, 2026
Implantation and Evaluation of Melanoma in the Murine Choroid via Optical Coherence Tomography
Published on: December 2, 2022
The biology of uveal melanoma
Adriana Amaro1, Rosaria Gangemi2, Francesca Piaggio1
1Laboratory of Molecular Pathology, Department of Integrated Oncology Therapies, IRCCS AOU San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, L.go Rosanna Benzi 10, 16132, Genoa, Italy.
Abstract:
Uveal melanoma (UM), a rare cancer of the eye, is distinct from cutaneous melanoma by its etiology, the mutation frequency and profile, and its clinical behavior including resistance to targeted therapy and immune checkpoint blockers. Primary disease is efficiently controlled by surgery or radiation therapy, but about half of UMs develop distant metastasis mostly to the liver. Survival of patients with metastasis is below 1 year and has not improved in decades. Recent years have brought a deep understanding of UM biology characterized by initiating mutations in the G proteins GNAQ and GNA11. Cytogenetic alterations, in particular monosomy of chromosome 3 and amplification of the long arm of chromosome 8, and mutation of the BRCA1-associated protein 1, BAP1, a tumor suppressor gene, or the splicing factor SF3B1 determine UM metastasis. Cytogenetic and molecular profiling allow for a very precise prognostication that is still not matched by efficacious adjuvant therapies. G protein signaling has been shown to activate the YAP/TAZ pathway independent of HIPPO, and conventional signaling via the mitogen-activated kinase pathway probably also contributes to UM development and progression. Several lines of evidence indicate that inflammation and macrophages play a pro-tumor role in UM and in its hepatic metastases. UM cells benefit from the immune privilege in the eye and may adopt several mechanisms involved in this privilege for tumor escape that act even after leaving the niche. Here, we review the current knowledge of the biology of UM and discuss recent approaches to UM treatment.
Insights
Uveal melanoma (UM), a rare eye cancer, differs from skin melanoma. While primary tumors are treatable, metastatic UM has poor survival, highlighting the need for new therapies.
Area of Science:
- Ophthalmology
- Oncology
- Cancer Biology
Background:
- Uveal melanoma (UM) is a rare eye cancer with distinct biology and poor prognosis for metastatic disease.
- Despite effective primary treatment, approximately 50% of UM patients develop liver metastasis with survival under one year.
- Recent advances reveal key genetic drivers, including GNAQ/GNA11 mutations, and cytogenetic alterations like chromosome 3 monosomy and chromosome 8q amplification.
Purpose of the Study:
- To review the current understanding of uveal melanoma biology.
- To discuss recent therapeutic approaches for uveal melanoma.
- To highlight the challenges in treating metastatic uveal melanoma.
Main Methods:
- Review of current scientific literature on uveal melanoma.
- Analysis of genetic and cytogenetic factors contributing to UM development and metastasis.
- Discussion of signaling pathways (G protein-YAP/TAZ, MAPK) and immune microenvironment roles.
Main Results:
- UM biology is characterized by GNAQ/GNA11 mutations, BAP1/SF3B1 mutations, and specific cytogenetic alterations.
- The YAP/TAZ and MAPK pathways are implicated in UM progression.
- Inflammation and macrophages play a pro-tumorigenic role, and UM utilizes immune privilege for tumor escape.
Conclusions:
- Precise prognostication is possible through molecular profiling, but effective adjuvant therapies are lacking.
- Understanding UM biology, including its unique signaling pathways and immune evasion strategies, is crucial for developing new treatments.
- Targeted therapies and immune checkpoint inhibitors have shown limited efficacy, necessitating novel therapeutic strategies for metastatic UM.
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