Antitumor activity of an enzyme prodrug therapy targeted to the breast tumor vasculature

Cancer Invest. 2013 Oct;31(8):505-10. doi: 10.3109/07357907.2013.840383.

Abstract

The L-methioninase-annexin V/selenomethionine enzyme prodrug system, designed to target the tumor vasculature and release the methylselenol anticancer drug in the tumor, was tested in mice with implanted MBA-MB-231 breast tumors. This therapy was able to cause a reduction in the size of the tumors during the treatment period. It was shown that L-methioninase-annexin V was uniformly bound at the blood vessel surface in the tumor and also that there was a substantial cutoff of blood flowing through the treated tumor, consistent with the therapy's design. This new approach for enzyme prodrug therapy of breast cancer appears promising.

Publication types

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

MeSH terms

  • Animals
  • Annexin A5 / metabolism*
  • Antineoplastic Agents / therapeutic use*
  • Breast Neoplasms / blood supply
  • Breast Neoplasms / drug therapy
  • Carbon-Sulfur Lyases / metabolism*
  • Cell Line, Tumor
  • Enzyme Therapy
  • Female
  • Humans
  • Mammary Neoplasms, Animal / blood supply
  • Mammary Neoplasms, Animal / drug therapy*
  • Methanol / analogs & derivatives*
  • Methanol / therapeutic use
  • Mice
  • Mice, SCID
  • Neoplasm Transplantation
  • Organoselenium Compounds / therapeutic use*
  • Prodrugs / metabolism
  • Prodrugs / therapeutic use
  • Selenomethionine / metabolism*

Substances

  • Annexin A5
  • Antineoplastic Agents
  • Organoselenium Compounds
  • Prodrugs
  • methaneselenol
  • Selenomethionine
  • Carbon-Sulfur Lyases
  • L-methionine gamma-lyase
  • Methanol