Abstract 1868: Targeting adenosine deaminase enhances anticancer effects of 3'-deoxyadenosine in uveal melanoma

Abstract

Abstract Uveal melanoma, which arises from melanocytes located in the uveal tract, is one of the most common primary intraocular cancers. GNAQ and GNA11 mutations, which are detected most of primary uveal melanoma, activate MAPK signaling pathway, increasing cancer cell proliferation, tumor progression and growth. BAP1 mutation is highly associated with liver metastasis and death. However, there are no good therapeutic compounds for uveal melanoma treatment in clinic. 3’-deoxyadenosine (cordycepin) is an adenosine analog which inhibits growth of several types of cancer. However, its anticancer effects have been showed in limited cancer cell lines. In addition, action mechanism of 3’deoxyadenosin is poorly understood. In this study, we found different adenosine deaminase (ADA) expression or activity affects different anticancer results in uveal melanoma. Inhibition of ADA using either siRNA or pharmacologic approaches sensitized tumors to 3’-deoxyadenosine in vitro and in vivo, resulting in increased apoptosis, reduced clonogenic capacity and slower migration of uveal melanoma cells in vitro. These potent ADA-dependent anti-tumor effects were also seen in various cancer cell lines. Therefore, we suggest the potential of adenosine deaminase (ADA) as both a biomarker predicting response to 3’-deoxyadenosine, and a target for combination therapy. Citation Format: Su-Chan Lee, Lujain Alaali, HyukJean Kwon, Mohammed Rigi, Charles G. Eberhart. Targeting adenosine deaminase enhances anticancer effects of 3'-deoxyadenosine in uveal melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1868.