Long pentraxin PTX3 as a novel treatment for fibroblast growth factor-8-mediated tumour diseases

Abstract

While prevailing strategies to treat cancer have concentrated on reducing or eliminating the tumour directly, recently treatments that affect tumour angiogenesis with inhibitors, particularly growth factor inhibitors, have been used in clinical trials. The inhibitors affect availability of growth factors and nutrients to the tumour and restrict access to blood vessels, which affects the spread of tumours to distal sites. This patent application proposes to use long pentraxin PTX3, or one of its derivatives, to treat cancers which are associated with abnormal expression of the fibroblast growth factor (FGF)-8 in ovarian, breast and prostate cancer. Abnormal expression of FGF-8 is associated with increased angiogenesis in tumours and mortality in cancer patients and stimulates growth of endothelial cells. The use of various formulations of PTX3 by itself or in combination with cytotoxic agents are proposed. The data presented shows that the addition of FGF-8 is able to partially inhibit the strong binding of another growth factor FGF-2, to PTX3 in vitro, indicating that PTX3 has affinity for FGF-8. This binding was specific, as the addition of another growth factor FGF-4, instead of FGF-8, had no effect. FGF-8 was shown to have mitogenic effects on an experimental epithelial cell line GM 7373. Addition of PTX3 was also able to inhibit this mitogenic effect. Whilst binding of PTX3 to this growth factor is intriguing, further studies are required to test PTX3 alone or in combination with other therapies to determine whether it may prove useful in selected cancer patients.

• angiogenesis
• breast
• FGF-8
• ovarian
• metastases
• pentraxin
• prostate
• PTX3
• tumour