Suramin is a polyanionic napthylurea used since the 1920s as an anti-parasitic agent. Recently, suramin was found to have antiretroviral and antitumor activities. It has been tested clinically in patients with AIDS, and has shown some antitumor activity in adrenocortical cancer, renal cancer and prostate cancer. Suramin binds tumor growth factors (e.g., epidermal growth factor, platelet derived growth factor) in vitro and thus potentially has a novel antitumor mechanism. The growth and differentiation of malignant melanoma is influenced by a number of growth factors including epidermal growth factor (EGF). Patients with advanced melanoma have poor clinical outcomes. A generally effective treatment with survival benefit is not available. Suramin has been tested in vitro, against fresh melanoma biopsy specimens in the Human Tumor Colony Forming Assay (HTCA) at the University of Arizona. Approximately 57% of the tumor specimens were sensitive (survival less than 30% of control). The in vitro results with suramin are much better than other agents commonly used to treat melanoma (DTIC, Cisplatin, vinca alkaloids, alpha interferon). The major hypothesis of this investigation is that suramin has antitumor activity against malignant melanoma. The objectives related to this hypothesis are to study suramin in a phase II clinical trial in patients with metastatic melanoma and to further test the in vitro suramin sensitivity of fresh melanoma biopsy specimens from patients entered on the clinical trial using the HTCA and the in vitro sensitivity of early passage melanoma cell lines using the HTCA and MTT assays. The relationship between in vitro suramin sensitivity and the clinical antitumor activity of suramin will be examined. The second hypothesis of this investigation is that the antitumor activity of suramin is mediated via its ability to bind tumor growth factors, such as EGF, thus interrupting a pathway of autocrine growth stimulation. Tumors with EGF growth dependence are expected to express the cell surface receptor for EGF. The major objective related to the second hypothesis will be to determine the frequency of expression at the EGF receptor on clinical melanoma specimens and the early passage melanoma cell lines using an anti-EGF receptor monoclonal antibody in flow cytometric and immunohistochemical methods. EGF receptor expression will be correlated with antitumor activity.
| Taylor, C W; Lui, R; Fanta, P et al. (1992) Effects of suramin on in vitro growth of fresh human tumors. J Natl Cancer Inst 84:489-94 |
