Regulators of Fibroblast Growth Factor Activity

TELEPHONE NUMBER: (314) 429-7700 AWARDEE NUMBER: 1 R43 CA61390-01 The overall objective is to develop polysulfated carbohydrate derivatives that will inhibit the action of fibroblast growth factors (FGF). FGF's have been implicated in several human cancers both as angiogenic factors and as growth factors capable of sustaining autonomous cell proliferation. Inhibition of these growth factors could inhibit tumor growth. The project is based on the preliminary observations that polysulfated carbohydrate derivatives, such as pentosan polysulfate, and polysulfated aromatic compounds, such as suramin, inhibit FGF activity and suppress the growth of cancer cells. Initial observations also indicate that heparin-like molecules are required for FGF activity. Specifically, we will synthesize related compounds from carbohydrates with FGF inhibitory activity. Since they are based on natural products, they may have fewer side affects than compounds such as suramin. The advantages of these compounds for clinical use would include ease of administration and chemical homogeneity.