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Fzd2 - novel anti-cancer therapeutic target

The role of β-catenin accumulation in the development of tumorigenicity has been well documented to date, with various mutations in β-catenin, APC, and axin genes typically to blame. Although β-catenin accumulation plays a role in hepatocellular carcinoma, mutations in the aforementioned genes are rare. This fact implicates the Wnt signaling pathway in HCC pathogenesis. To date, it has been unknown which Wnt ligands and/or FZD receptors are responsible for the activation of the β-catenin pathway in HCC. Here, we outline the role of Fzd2 in up-regulation of β-catenin production and subsequent hepatocellular carcinoma, breast, lung, colon, and ovarian cancer development.

Research within the laboratory of Gavin Macbeath in Systems Biology at Harvard Medical School points to the role of the Wnt pathway in β -catenin accumulation, and Fzd2 specifically as a potential therapeutic target against liver cancer. Research show that Fzd2 knockdowns reduce tumor growth in nude mice, reduction in Fzd2 activity via knockdown or antibody treatment results in reduced metastasis, and anti-Fzd2 treatment causes internalization of cell surface Fzd2 receptors.

Intellectual Property Status: Patent(s) Pending

Applications

The invention describes methods of treatment of cancer with a therapeutic antibody directed against Fzd2. More specifically, this technology may prove efficacious in the treatment of poorly differentiated hepatocellular carcinomas, which represents 85% of all primary liver cancers and has a rising global incidence. Fzd2 expression is also correlated with the development of the mesenchymal phenotype in breast, lung, colon, and ovarian cancer cell lines, suggesting a potential role in broader tumor pathogenesis.

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