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Discovery of a small molecule that inhibits Bcl-3-mediated cyclin D1 expression in melanoma cells.


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.

SUBMITTER: Saamarthy K 

PROVIDER: S-EPMC10795364 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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Discovery of a small molecule that inhibits Bcl-3-mediated cyclin D1 expression in melanoma cells.

Saamarthy Karunakar K   Ahlqvist Kristofer K   Daams Renée R   Balagunaseelan Navisraj N   Rinaldo-Matthis Agnes A   Kazi Julhash U JU   Sime Wondossen W   Massoumi Ramin R  

BMC cancer 20240118 1


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.  ...[more]

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