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BioDrugs

, Volume 22, Issue 1, pp 53–58 | Cite as

Ribonucleases as Novel Chemotherapeutics

The Ranpirnase Example
  • J. Eugene Lee
  • Ronald T. Raines
Novel Therapeutic Strategies

Abstract

Ranpirnase, a cytotoxic ribonuclease from the frog Rana pipiens, is the archetype of a novel class of cancer chemotherapeutic agents based on homologs and variants of bovine pancreatic ribonuclease (RNase A). Ranpirnase in combination with doxorubicin is in clinical trials for the treatment of unresectable malignant mesothelioma and other cancers. The putative mechanism for ranpirnase-mediated cytotoxicity involves binding to anionic components of the extracellular membrane, cytosolic internalization, and degradation of transfer RNA leading to apoptosis. The maintenance of ribonucleolytic activity in the presence of the cytosolic ribonuclease inhibitor protein is a key aspect of the cytotoxic activity of ranpirnase. The basis for its specific toxicity for cancer cells is not known. This review describes the development of ranpirnase as a cancer chemotherapeutic agent.

Keywords

Malignant Mesothelioma Conformational Stability Rana Pipiens Cancer Chemotherapeutic Agent Northern Leopard Frog 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

Work in the Raines laboratory on ribonucleases is supported by grant CA073808 (NIH). We are grateful to R.F. Turcotte and T.-Y. Chao for comments on the manuscript. The authors have no conflicts of interest that are directly relevant to the content of this review.

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© Adis Data Information BV 2008

Authors and Affiliations

  1. 1.Department of BiochemistryUniversity of Wisconsin-MadisonMadisonUSA
  2. 2.Division of BiologyCalifornia Institute of TechnologyPasadenaUSA
  3. 3.Department of ChemistryUniversity of Wisconsin-MadisonMadisoncUSA

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