1. Discovery of a small molecule that inhibits Bcl-3-mediated cyclin D1 expression in melanoma cells.
- Author
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Saamarthy K, Ahlqvist K, Daams R, Balagunaseelan N, Rinaldo-Matthis A, Kazi JU, Sime W, and Massoumi R
- Subjects
- Male, Animals, Humans, Cyclin D1 metabolism, Proto-Oncogene Proteins c-bcl-2 genetics, Proto-Oncogene Proteins c-bcl-2 metabolism, Cell Proliferation, Cell Line, Tumor, Apoptosis, Melanoma pathology, Skin Neoplasms pathology
- Abstract
Molecular targeted therapy using a drug that suppresses the growth and spread of cancer cells via inhibition of a specific protein is a foundation of precision medicine and treatment. High expression of the proto-oncogene Bcl-3 promotes the proliferation and metastasis of cancer cells originating from tissues such as the colon, prostate, breast, and skin. The development of novel drugs targeting Bcl-3 alone or in combination with other therapies can cure these patients or prolong their survival. As a proof of concept, in the present study, we focused on metastatic melanoma as a model system. High-throughput screening and in vitro experiments identified BCL3ANT as a lead molecule that could interfere with Bcl-3-mediated cyclin D1 expression and cell proliferation and migration in melanoma. In experimental animal models of melanoma, it was demonstrated that the use of a Bcl-3 inhibitor can influence the survival of melanoma cells. Since there are no other inhibitors against Bcl-3 in the clinical pipeline for cancer treatment, this presents a unique opportunity to develop a highly specific drug against malignant melanoma to meet an urgent clinical need., (© 2024. The Author(s).)
- Published
- 2024
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