New targeted and epigenetic therapeutic strategies for the treatment of uveal melanoma.
Alexander Z WeiAshray B ManiarRichard D CarvajalPublished in: Cancer gene therapy (2022)
Uveal melanoma (UM) is a rare, genetically bland ocular malignancy with excellent local treatment options, but no disease-specific therapies are approved for use in the metastatic setting by the Food and Drug Administration. Metastatic UM (mUM) confers a prognosis of ~15 months. Unlike cutaneous melanoma, UM is poorly responsive to checkpoint inhibitors and cytotoxic chemotherapy highlighting the importance of clarifying vulnerable disease-specific mechanisms, such as cell cycle or metabolic pathways necessary for tumor growth and survival. The elucidation of signaling pathways downstream of the frequently mutated GNA GTPase such as PKC/MAPK/ERK/MEK, PI3K/AKT, and YAP-Hippo have offered potential targets. Potentially druggable epigenetic targets due to BAP1-mutated UM have also been identified, including proteins involved with histone deacetylation and DNA splicing. This review describes the preclinical rationale for the development of targeted therapies and current strategies currently being studied in clinical trials or will be in the near future.
Keyphrases
- pi k akt
- cell cycle
- cell proliferation
- signaling pathway
- drug administration
- dna methylation
- clinical trial
- cell cycle arrest
- squamous cell carcinoma
- small cell lung cancer
- skin cancer
- gene expression
- cancer therapy
- epithelial mesenchymal transition
- dna damage
- basal cell carcinoma
- human health
- oxidative stress
- stem cells
- combination therapy
- cell free
- drug delivery
- mesenchymal stem cells
- randomized controlled trial
- protein kinase
- double blind