Efficacy of suramin against human prostate carcinoma DU145 xenografts in nude mice

Abstract

Suramin, without concomitant corticosteroid therapy, was effective in slowing the growth of DU145 xenografts in nude mice at clinically relevant plasma suramin levels. The data showing efficacy for DU145 xenografts was supported by the lack of efficacy at the same time for xenografts of cells known to be less responsive to suramin in vitro, i.e. the SR DU145 cells, at similar doses and nadir plasma suramin levels. In discussions on the utility of suramin our data should be considered as support for continuing the study of suramin in the treatment of advanced, androgen-independent prostate cancer.

Sodium Stibogluconate Is a Potent Inhibitor of Protein Tyrosine Phosphatases and Augments Cytokine Responses in Hemopoietic Cell Lines

“…Moreover, the drug by itself may have therapeutic effects through inhibiting PTPases to change the balance of intracellular tyrosine phosphorylation that controls cell proliferation, differentiation and functional activities. Suramin is presently being evaluated in clinical trials for the treatment of prostate cancer and other solid tumors (51). Because sodium stibogluconate appeared to be a more efficient inhibitor of PTPases than suramin, it has the potential to become a better drug for effective treatment of these diseases.…”

Pharmacodynamics of Telomerase Inhibition and Telomere Shortening by Noncytotoxic Suramin

“…This, in turn, sparked considerable interests and efforts in developing it as a conventional cytotoxic agent [17]. In mouse tumor models [18][19][20], antitumor activity of suramin was observed at doses between 100 and 260 mg/kg per week with corresponding plasma concentrations exceeding 100 μM. Clinically, suramin was evaluated in a wide variety of solid tumors, either as single agent or in combination with other chemotherapeutics, and showed modest activity at plasma concentrations of 100-250 μM; these cytotoxic concentrations resulted in significant toxicities (summarized in 21).…”