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Investigational New Drugs

, Volume 26, Issue 1, pp 1–5 | Cite as

INO-1001, a novel inhibitor of poly(ADP-ribose) polymerase, enhances tumor response to doxorubicin

  • Kathryn A. Mason
  • David Valdecanas
  • Nancy R. Hunter
  • Luka Milas
PRECLINICAL STUDIES

Summary

Poly(ADP-ribose) synthetase inhibitor, INO-1001, is known to sensitize cells to radiation in vitro by inhibiting the repair of DNA damage. Recent evidence has suggested that PARP inhibition may also be a way of selectively targeting p53 deficient cancer cells. The present study tested INO-1001 for its in vivo effect on the chemoresponse of two p53 deficient tumors, human breast cancer MDA-MB-231 and murine mammary carcinoma MCa-K. Doxorubicin was used as the DNA damaging agent and tumor growth delay assay was used as the endpoint. Results showed that INO-1001 was highly effective in enhancing the anti-tumor effects of Doxorubicin for both MDA-MB-231 (EF = 1.88) and MCa-K (EF = 1.64). We conclude that PARP inhibitor INO-1001 has high potential for enhancing the anti-tumor effects of chemotherapy agents such as Doxorubicin against p53 deficient breast cancer.

Keywords

Poly(ADP-ribose) INO-1001 Doxorubicin p53-Deficient cancer cells Doxorubicin-induced apoptosis 

Notes

Acknowledgement

Sponsored by a Laboratory Study Agreement with Inotek Pharmaceuticals Corp and NIH Grants CA06294 and CA16672.

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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Kathryn A. Mason
    • 1
  • David Valdecanas
    • 1
  • Nancy R. Hunter
    • 1
  • Luka Milas
    • 1
  1. 1.Department of Experimental Radiation OncologyThe University of Texas M. D. Anderson Cancer CenterHoustonUSA

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