Combination of YAP inhibition and photodynamic therapy induces dual DNA damage and activates STING pathway to enhance immunotherapy in uveal melanoma.

ABSTRACT: Uveal melanoma (UM) is the most common primary intraocular malignancy in adults and is highly aggressive, with no therapies shown to improve overall survival. Although immunotherapy achieves response rates of 33-40 % in advanced cutaneous melanoma, its efficacy in UM is disappointingly low, with only 3.6 % of patients responding. Herein, we report a nanomedicine-based strategy to enhance immunotherapy efficacy in UM by strong activation of the cyclic guanosine 3',5'-cyclic monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) pathway through dual deoxyribonucleic acid (DNA) damage induced by Yes-associated protein (YAP) inhibition and photodynamic therapy (PDT). This approach, using hyaluronic acid nanoparticle (HANP)-formulated verteporfin (HANP/VP),

SUBMITTER: Zhang S 

PROVIDER: S-EPMC12754387 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature