Enhancing Chemotherapy Efficacy: Insights into the Role of S44563 in Uveal Melanoma Treatment

3 June 2024
The study focuses on uveal melanoma (UM), a common eye cancer in adults that often leads to liver metastases and has a poor prognosis due to limited treatment options. The research investigates the role of Bcl-2 family proteins, which are highly expressed in human uveal melanomas and could be a target for new therapies. The Bcl-2/Bcl-XL inhibitor S44563 was tested on primary human UM xenografts, either alone or in combination with chemotherapy drug fotemustine.

Four primary UM models were used in the experiments, sourced from patients who underwent eye removal or liver metastasis surgery. S44563 was administered at two dosages, either alone or in combination with fotemustine, and its effects were measured through Tumor Growth Inhibition (TGI). Immunohistochemistry was used to assess the expression of Bcl-2, Bcl-XL, and Mcl-1 proteins after treatment.

Results indicated that S44563 alone had a moderate effect on tumor growth in one model, but when combined with fotemustine, it showed synergistic activity in two models. Additionally, the combination therapy delayed tumor growth in two out of three tested xenografts. However, the expression levels of the Bcl-2 family proteins were not altered by S44563 treatment.

The conclusion emphasizes the potential of S44563 as a new therapeutic agent for UM, particularly when used in combination with chemotherapy, despite its limited efficacy when used alone. The study's findings were presented at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in 2011.

How to Use Synapse Database to Search and Analyze Translational Medicine Data?

The transational medicine section of the Synapse database supports searches based on fields such as drug, target, and indication, covering the T0-T3 stages of translation. Additionally, it offers a historical conference search function as well as filtering options, view modes, translation services, and highlights summaries, providing you with a unique search experience.

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Taking obesity as an example, select "obesity" under the indication category and click search to enter the Translational Medicine results list page. By clicking on the title, you can directly navigate to the original page.

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By clicking the analysis button, you can observe that GLP-1R treatment for obesity has gained significant attention over the past three years, with preclinical research still ongoing in 2023. Additionally, there are emerging potential targets, such as GDF15, among others.

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