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Efficacy and comparative effectiveness of sirolimus as an anticancer drug

Authors

  • Melissa Hu MD,

    1. Department of Otolaryngology–Head and Neck Surgery, Louisiana State University Health Sciences Center, Shreveport, Louisiana, U.S.A
    2. Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, Louisiana, U.S.A
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  • Oleksandr Ekshyyan PhD,

    1. Department of Otolaryngology–Head and Neck Surgery, Louisiana State University Health Sciences Center, Shreveport, Louisiana, U.S.A
    2. Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, Louisiana, U.S.A
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  • Lilantha Herman Ferdinandez MD,

    1. Department of Otolaryngology–Head and Neck Surgery, Louisiana State University Health Sciences Center, Shreveport, Louisiana, U.S.A
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  • Xiaohua Rong BS,

    1. Department of Otolaryngology–Head and Neck Surgery, Louisiana State University Health Sciences Center, Shreveport, Louisiana, U.S.A
    2. Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, Louisiana, U.S.A
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  • Gloria Caldito PhD,

    1. Department of Biometry, Louisiana State University Health Sciences Center, Shreveport, Louisiana, U.S.A
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  • Cherie-Ann O. Nathan MD, FACS

    Corresponding author
    1. Department of Otolaryngology–Head and Neck Surgery, Louisiana State University Health Sciences Center, Shreveport, Louisiana, U.S.A
    2. Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, Louisiana, U.S.A
    • Department of Otolaryngology–Head and Neck Surgery, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130-3932
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  • This study was supported by grant no. R01CA102363 from the National Cancer Institute to Dr. Nathan. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. The authors have no other funding, financial relationships, or conflicts of interest to disclose.

Abstract

Objectives/Hypothesis:

To evaluate antitumor efficacy of the generic mammalian target of rapamycin (mTOR) inhibitor sirolimus in preclinical animal models of head and neck squamous cell carcinoma (HNSCC) and compare its effects with those of the patented analogue temsirolimus.

Study Design:

In vivo study.

Methods:

To develop xenograft established tumor model (ETM) of HNSCC, FaDu cells were injected subcutaneously into nude mice. When tumors reached 50 to 60 mm3, mice were randomized into five groups and treated daily intraperitoneally with sirolimus at various doses for 5 days per week for 3 weeks. Tumor volumes were measured. The results were compared with historical data on temsirolimus effects. In the minimal residual disease (MRD) model, surgical wounds were created and FaDu cells implanted. After 72 hours, animals were randomized into two groups and were injected intraperitoneally with 0 or 5 mg/kg sirolimus for 5 days per week for 30 days.

Results:

In the ETM, sirolimus significantly inhibited tumor growth (P < .01), although there was no overall significant difference in tumor growth inhibition between sirolimus and temsirolimus. In the MRD model, sirolimus significantly suppressed growth of tumors (P < .001) and improved survival compared with controls (P < .01). There was a significant decrease in pS6 expression, indicating mTOR inhibition.

Conclusions:

In this study, we demonstrate that the generic mTOR inhibitor sirolimus shows potent antitumor activity in HNSCC and produces comparable effects to the patent drug temsirolimus. Sirolimus has the potential of serving as an economic and comparative targeted agent to temsirolimus in the treatment of HNSCC.

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