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PI-88: a novel inhibitor of angiogenesis

Ragini Kudchadkar1, Rene Gonzalez, Karl D Lewis

  • 1University of Colorado Cancer Center, Aurora, CO 80045, USA. karl.Lewis@uchsc.edu

Expert Opinion on Investigational Drugs
|October 17, 2008
PubMed

Insights

PI-88, an investigational anti-cancer drug, inhibits heparanase to block tumor angiogenesis. Early trials show promise in melanoma and liver cancer, but side effects like thrombocytopenia require further study.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Angiogenesis, the formation of new blood vessels, is crucial for tumor growth and survival.
  • Current anti-angiogenic therapies, including antibodies and kinase inhibitors, offer modest benefits in various solid tumors.
  • There is a need for novel anti-angiogenic agents with different mechanisms of action.

Purpose of the Study:

  • To evaluate the efficacy and safety of PI-88, a novel heparanase inhibitor, as an anti-cancer therapeutic.
  • To investigate the mechanism of action of PI-88 in blocking tumor angiogenesis.

Main Methods:

  • PI-88 was administered to patients in Phase I/II clinical trials.
  • The study assessed the drug's effect on angiogenesis through various cellular and biological markers.
  • Tumor response and adverse events, including thrombocytopenia, were monitored.

Main Results:

  • PI-88 demonstrated promising results in patients with melanoma and hepatocellular carcinoma.
  • The drug effectively inhibits heparanase, blocking angiogenesis on multiple levels.
  • Antibody-induced thrombocytopenia was identified as a dose-limiting toxicity in some patients.

Conclusions:

  • PI-88 represents a novel therapeutic strategy targeting tumor angiogenesis by inhibiting heparanase.
  • The drug shows potential in treating various cancers, particularly melanoma and hepatocellular carcinoma.
  • Further research is needed to manage and mitigate side effects such as thrombocytopenia for broader clinical application.

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