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Claudell Cox, MD; Sofia D. Merajver, MD, PhD; Sirius Yoo, MS; Robert D. Dick, BS; George J. Brewer, MD; Julia Shin-Jung Lee, MS; Theodoros N. Teknos, MD

Arch Otolaryngol Head Neck Surg. 2003;129:781-785.

Objective  To determine whether long-term therapy with tetrathiomolybdate suppresses tumor growth in an animal model.

Design  In vivo murine model.

Subjects  Thirteen 8-week-old C3H/HeJ mice, randomly assigned to a tetrathiomolybdate treatment group (n = 7) or a control group (n = 6).

Interventions  To render the treatment group mice copper deficient, tetrathiomolybdate (0.7 mg/d per mouse) was added to their drinking water on days 1 through 20. Control group mice received only fresh drinking water. A flank injection of 1.5 x 10⁵ SCCVII/SF cells was administrated to all mice on day 21. The treatment group mice continued to receive daily tetrathiomolybdate throughout the remainder of the experiment (70 days). Tumor volume measurements (square of the width x length x 0.52) were taken every other day beginning on day 40.

Main Outcome Measures  Mean tumor volume differences.

Results  Mean ± SD tumor volumes on day 40 were 146 ± 263 mm³ (n = 7) and 274 ± 331 mm³ (n = 6) for the treatment and control groups, respectively. By day 54, the mean tumor volume for the treatment group was 65 ± 0 mm³, compared with 1716 ± 960 mm³ for the control group (P<.001). Treatment was withheld on day 54, resulting in a dramatic increase in tumor growth in the treatment group mice such that by day 60, there was no significant difference in mean tumor volume between groups.

Conclusion  This study demonstrates the ability of tetrathiomolybdate to maintain a significant and reversible suppression of long-term tumor growth in this murine model of squamous cell carcinoma, suggesting a potential application for the use of tetrathiomolybdate in human squamous cell carcinoma.

From the Departments of Otolaryngology–Head and Neck Surgery (Drs Cox and Teknos), Hematology/Oncology (Dr Merajver), Human Genetics (Mr Dick and Dr Brewer), and Biomedical Statistics (Ms Lee) and the Medical School (Mr Yoo), University of Michigan Health System, Ann Arbor. Drs Merajver and Brewer and Mr Dick hold equity interest in Attenuon, San Diego, Calif; Drs Merajver and Brewer are also consultants for Attenuon.

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