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Cancer Chemotherapy and Pharmacology

, Volume 66, Issue 1, pp 1–9 | Cite as

Ruthenium-based chemotherapeutics: are they ready for prime time?

  • Emmanuel S. Antonarakis
  • Ashkan Emadi
Mini Review

Abstract

Since the discovery of cis-platinum, many transition metal complexes have been synthesized and assayed for antineoplastic activity. In recent years, ruthenium-based molecules have emerged as promising antitumor and antimetastatic agents with potential uses in platinum-resistant tumors or as alternatives to platinum. Ruthenium compounds theoretically possess unique biochemical features allowing them to accumulate preferentially in neoplastic tissues and to convert to their active state only after entering tumor cells. Intriguingly, some ruthenium agents show significant activity against cancer metastases but have minimal effects on primary tumors. Two ruthenium-based drugs, NAMI-A and KP1019, have reached human clinical testing. This review will highlight the chemical properties, mechanism of action, preclinical data, and early phase clinical results of these two lead ruthenium compounds. Other promising ruthenium agents will also be reviewed with emphasis on the novel ruthenium compound ONCO4417, and DW1/2 that has demonstrated Pim-1 kinase inhibition in preclinical systems. Further development of these and other ruthenium agents may rely on novel approaches including rational combination strategies as well as identification of potential pharmacodynamic biomarkers of drug activity aiding early phase clinical studies.

Keywords

Ruthenium Chemotherapy NAMI-A KP1019 ONCO4417 

Notes

Conflict of interest statement

The authors indicate no financial or other conflicts of interest.

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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  1. 1.Sidney Kimmel Comprehensive Cancer CenterJohns Hopkins UniversityBaltimoreUSA

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