Toward Precision Medicine: Gene Therapy Applications in the Management of Uveal Melanoma

Uveal melanoma (UM) is the prevailing malignant tumor that develops within the eye in adults, and it has a bleak outlook because of the few treatment choices available and the high likelihood of returning after treatment. Currently, surgical intervention, radiation therapy, and a combination of both modalities are available therapeutic modalities for controlling UM. However, these techniques are associated with notable adverse effects and have limited efficacy. Therefore, there is a lack of sufficient and reliable therapies for UM, especially for advanced and metastatic UM forms. This review aims to summarize the clinical features and current therapies of UM and highlight recent progress in gene therapy approaches.

Significant developments in gene therapy have introduced multiple strategies for targeting UM. Gene silencing using siRNA and shRNA has shown efficacy in downregulating oncogenic pathways. CRISPR/Cas9-based editing has enabled selective disruption of tumor-promoting genes, sensitizing tumor cells to targeted inhibitors. Restoration of tumor-suppressive miRNAs has reduced proliferation, migration, and invasion of UM cells in preclinical models. Suicide gene therapy has demonstrated potent cytotoxicity in xenografts. Moreover, oncolytic viruses and stem-cell-associated delivery systems provide novel mechanisms for tumor-selective gene expression and immune activation. Although challenges persist-such as delivery efficiency, immune responses, and genetic heterogeneity-ongoing innovations in vector design, non-viral nanoformulations, and mutation-guided therapies continue to enhance clinical feasibility.

Gene therapy provides improved safety profiles and the possibility of tailored treatment strategies by integrating information on gene expression patterns and DNA alterations. In the future, gene therapy has the potential to improve the treatment of UM by targeting specific genetic mutations driving tumor growth and may offer new hope for patients with advanced stages of UM.