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

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.