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New Drugs

Bryostatin-1: A Novel PKC Inhibitor in Clinical Development

, M.D. & , M.D.
Pages 924-936 | Published online: 12 Oct 2003
 

Abstract

Modulation of PKC represents a novel approach to cancer therapy. Bryostatin-1 is a macrocyclic lactone derived from a marine invertebrate that binds to the regulatory domain of protein kinase C. Short-term exposure to bryostatin-1 promotes activation of PKC, whereas prolonged exposure promotes significant downregulation of PKC. In numerous hematological and solid tumor cell lines, bryostatin-1 inhibits proliferation, induces differentiation, and promotes apoptosis. Furthermore, preclinical studies indicate that bryostatin-1 potently enhances the effect of chemotherapy. In many cases, this effect is sequence specific. Bryostatin-1 is currently in phase I and phase II clinical trials. The major toxicities are myalgias, nausea, and vomiting. Although there is minimal single-agent activity, combinations with standard chemotherapy are providing very encouraging results and indicate a new direction in cancer therapy.

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