Abstract LB173: A bioinformatics approach to determine the potential benefit of blocking both Galectin-1 and Galectin-3 in cancer

Abstract

Abstract Galectins are a family of Beta-galactoside-binding lectins that control numerous cellular processes in health and disease, including fibrosis, carcinogenesis and tumour immune evasion. Evidence is starting to emerge that blockade of more than one galectin may provide additional benefit within the oncology arena due to the overlapping biological functions associated with these lectins. Due to the rich and robust external datasets associated with the two most previously studied galectins, we initially investigated the potential therapeutic benefit of a dual blockade approach of Galectin-1 (Gal-1) and Galectin-3 (Gal-3). A systematic assessment, consisting of three steps, was implemented to conclude the potential clinical effects of dual Gal-1 and Gal-3 inhibition and the specific cancers which may benefit the most from this approach. Step 1 consisted of pathway map reconstructions, depicting the role of Gal-1 and Gal-3 in tumor invasion, metastasis and angiogenesis, to confirm overlapping and independent cancer pathways associated with both galectins. These maps were constructed based on evidence from published literature and additional external databases. Step 2 aligned and ranked the associated expression of Gal-1 and Gal-3 at both the mRNA and protein level across different cancer types. This profiling included data from publicly available TCGA and CPTAC databases and additional external sources. Step 3 tested the highest ranked Gal-1 and Gal-3 mRNA and protein expressing cancers for association of survival by stratifying patients into four cohorts: Gal-1 low/Gal-3 low, Gal-1 high/Gal-3 low, Gal-1 low/Gal-3 high, Gal-1 high/Gal-3 high. Survival profiles quite clearly show that high expression of both galectins leads to poor survival in certain cancer types but not all. To summarize, using a bioinformatics approach, we have provided the initial evidence that Gal-1 and Gal-3 are highly expressed at both the gene and protein level in several cancers with their combined expression strongly correlating with poor survival rates. This data suggests, in certain cancer types, that targeting dual inhibition of Gal-1 and Gal-3 will have the potential to improve patient survival to a greater extent than a single Galectin blockade approach. Citation Format: Ian Holyer, Rob Slack. A bioinformatics approach to determine the potential benefit of blocking both Galectin-1 and Galectin-3 in cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB173.