Investigational New Drugs

, Volume 14, Issue 2, pp 161–167

Efficacy of HMAF (MGI-114) in the MV522 metastatic lung carcinoma xenograft model nonresponsive to traditional anticancer agents

  • Michael J. Kelner
  • Trevor C. McMorris
  • Leita Estes
  • Wen Wnag
  • Kyra M. Samson
  • Raymond Taetle
Preclinical Studies

DOI: 10.1007/BF00210787

Cite this article as:
Kelner, M.J., McMorris, T.C., Estes, L. et al. Invest New Drugs (1996) 14: 161. doi:10.1007/BF00210787
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Summary

Illudin analogs are cytotoxic to a variety of multidrug resistant cell lines, and display an unusual toxicity towards DNA helicase-deficient cell lines. Earlier illudin analogs demonstrated efficacy in several xenograft models, including a metastatic MV522 lung cancer model, resistant to conventional anticancer agents. These illudin analogs prolonged life span as compared to conventional agents, but did not induce complete remission of primary tumors. In vitro screening studies identified a semisynthetic derivative, hydroxymethylacylfulvene (HMAF, MGI-114), with increased selective cytotoxicity towards carcinoma cells. The HMAF analog was markedly effective in the experimental MV522 metastasizing lung carcinoma xenograft system, a model refractory to treatment with existing anticancer agents. Treatment with paclitaxel, doxorubicin, or cisplatin failed to significantly inhibit primary tumor growth or prolong life span of MV522 tumor-bearing animals. Treatment with mitomycin C at the LD20 increased life span in surviving animals up to 61% (p = 0.04). Treatment with HMAF induced primary tumor regression in all animals and increased life span greater than 150% (p<0.001). Thus, administration of HMAF inhibited development of lung metastasis in a model refractory to treatment with conventional anticancer agents. These results support further evaluation of HMAF as a therapeutic agent for treatment of solid tumors such as adenocarcinoma of the lung.

Key words

illudin HMAF xenograft adenocarcinoma 

Copyright information

© Kluwer Academic Publishers 1996

Authors and Affiliations

  • Michael J. Kelner
    • 1
  • Trevor C. McMorris
    • 2
  • Leita Estes
    • 1
  • Wen Wnag
    • 2
  • Kyra M. Samson
    • 1
  • Raymond Taetle
    • 3
  1. 1.Department of PathologyUCSDSan DiegoUSA
  2. 2.Department of ChemistryUCSDSan DiegoUSA
  3. 3.Arizona Cancer Center, University of ArizonaTucsonUSA
  4. 4.Department of Pathology 8320University of California, San Diego, Medical CenterSan DiegoUSA

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