Bryostatin-1: a novel PKC inhibitor in clinical development

Cancer Invest. 2003;21(6):924-36. doi: 10.1081/cnv-120025095.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacology*
  • Apoptosis*
  • Bryostatins
  • Cell Differentiation
  • Clinical Trials, Phase I as Topic
  • Clinical Trials, Phase II as Topic
  • Down-Regulation
  • Humans
  • Lactones / adverse effects
  • Lactones / pharmacology*
  • Macrolides
  • Nausea / chemically induced
  • Pain / chemically induced
  • Protein Kinase C / biosynthesis
  • Protein Kinase C / metabolism*
  • Vomiting / chemically induced


  • Antineoplastic Agents
  • Bryostatins
  • Lactones
  • Macrolides
  • bryostatin 1
  • Protein Kinase C