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Isolated Hepatic Perfusion as a Treatment for Liver Metastases of Uveal Melanoma
Published on: January 25, 2015
Emerging therapeutic strategies for metastatic uveal melanoma: Targeting driver mutations
Xiao-Lian Liu1,2, Zhou Run-Hua2, Jing-Xuan Pan3
1Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Abstract:
Uveal melanoma (UM) is the most common primary malignant intraocular tumor in adults. Although primary UM can be effectively controlled, a significant proportion of cases (40% or more) eventually develop distant metastases, commonly in the liver. Metastatic UM remains a lethal disease with limited treatment options. The initiation of UM is typically attributed to activating mutations in GNAQ or GNA11. The elucidation of the downstream pathways such as PKC/MAPK, PI3K/AKT/mTOR, and Hippo-YAP have provided potential therapeutic targets. Concurrent mutations in BRCA1 associated protein 1 (BAP1) or splicing factor 3b subunit 1 (SF3B1) are considered crucial for the acquisition of malignant potential. Furthermore, in preclinical studies, actionable targets associated with BAP1 loss or oncogenic mutant SF3B1 have been identified, offering promising avenues for UM treatment. This review aims to summarize the emerging targeted and epigenetic therapeutic strategies for metastatic UM carrying specific driver mutations and the potential of combining these approaches with immunotherapy, with particular focus on those in upcoming or ongoing clinical trials.
Insights
Metastatic uveal melanoma (UM) is a lethal cancer with few treatments. This review highlights new targeted therapies and epigenetic strategies for UM with specific mutations, exploring combinations with immunotherapy.
Area of Science:
- Ophthalmology
- Oncology
- Genetics
Background:
- Uveal melanoma (UM) is the most common primary adult intraocular malignancy.
- While primary UM is often controllable, over 40% metastasize, frequently to the liver, leading to a poor prognosis.
- Metastatic UM presents limited therapeutic options.
Purpose of the Study:
- To review emerging targeted and epigenetic therapies for metastatic UM.
- To explore the potential of combining these strategies with immunotherapy.
- To focus on treatments relevant to ongoing or upcoming clinical trials.
Main Methods:
- Review of current literature on uveal melanoma pathogenesis and treatment.
- Analysis of genetic drivers including GNAQ/GNA11, BAP1, and SF3B1 mutations.
- Examination of downstream pathways (PKC/MAPK, PI3K/AKT/mTOR, Hippo-YAP) and their therapeutic implications.
Main Results:
- Activating mutations in GNAQ or GNA11 initiate UM.
- Concurrent mutations in BAP1 or SF3B1 are critical for malignant progression.
- Preclinical studies identify actionable targets for BAP1 loss and SF3B1 mutations.
Conclusions:
- Targeted therapies and epigenetic strategies show promise for metastatic UM.
- Combination approaches, including immunotherapy, are being investigated.
- Clinical trials are evaluating novel treatment strategies for specific UM genetic profiles.
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