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Published on: November 8, 2015
Efficacy and comparative effectiveness of sirolimus as an anticancer drug
Melissa Hu1, Oleksandr Ekshyyan, Lilantha Herman Ferdinandez
1Department of Otolaryngology-Head and Neck Surgery, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130-3932, USA.
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 mm(3), 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.
Insights
Generic sirolimus demonstrates potent antitumor effects in head and neck squamous cell carcinoma (HNSCC) models, comparable to the patented temsirolimus. This suggests sirolimus as a cost-effective targeted therapy option for HNSCC.
Area of Science:
- Oncology
- Pharmacology
- Cancer Research
Background:
- Head and neck squamous cell carcinoma (HNSCC) remains a significant health challenge.
- Targeted therapies, such as mammalian target of rapamycin (mTOR) inhibitors, offer promising treatment avenues.
- Sirolimus, a generic mTOR inhibitor, presents a potential cost-effective alternative to patented analogues like temsirolimus.
Purpose of the Study:
- To evaluate the antitumor efficacy of sirolimus in preclinical HNSCC models.
- To compare the efficacy of sirolimus with temsirolimus in HNSCC.
- To assess sirolimus's potential as an economical targeted therapy for HNSCC.
Main Methods:
- In vivo study utilizing xenograft established tumor models (ETM) and minimal residual disease (MRD) models in nude mice.
- Daily intraperitoneal administration of sirolimus in ETM and MRD models.
- Tumor volume measurement and survival analysis, with comparison to historical temsirolimus data.
Main Results:
- Sirolimus significantly inhibited tumor growth in both ETM and MRD models (P < .01 and P < .001, respectively).
- Sirolimus demonstrated comparable tumor growth inhibition to temsirolimus in the ETM.
- Sirolimus significantly improved survival in the MRD model (P < .01) and reduced pS6 expression, confirming mTOR inhibition.
Conclusions:
- Generic sirolimus exhibits potent antitumor activity against HNSCC in preclinical models.
- Sirolimus's efficacy is comparable to the patented drug temsirolimus.
- Sirolimus represents a viable, economical, and effective targeted therapeutic option for HNSCC treatment.
