Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comparative Study
. 2008 Jan 28:8:1.
doi: 10.1186/1471-5945-8-1.

Topical rapamycin inhibits tuberous sclerosis tumor growth in a nude mouse model

Aubrey Rauktys  1 , Nancy Lee, Laifong Lee, Sandra L Dabora
Affiliations
Comparative Study

Topical rapamycin inhibits tuberous sclerosis tumor growth in a nude mouse model

Aubrey Rauktys et al. BMC Dermatol. .

Abstract

Background: Skin manifestations of Tuberous Sclerosis Complex (TSC) cause significant morbidity. The molecular mechanism underlying TSC is understood and there is evidence that systemic treatment with rapamycin or other mTOR inhibitors may be a useful approach to targeted therapy for the kidney and brain manifestations. Here we investigate topical rapamycin in a mouse model for TSC-related tumors.

Methods: 0.4% and 0.8% rapamycin ointments were applied to nude mice bearing subcutaneous, TSC-related tumors. Topical treatments were compared with injected rapamycin and topical vehicle. Rapamycin levels in blood and tumors were measured to assess systemic drug levels in all cohorts.

Results: Treatment with topical rapamycin improved survival and reduced tumor growth. Topical rapamycin treatment resulted in systemic drug levels within the known therapeutic range and was not as effective as injected rapamycin.

Conclusion: Topical rapamycin inhibits TSC-related tumor growth. These findings could lead to a novel treatment approach for facial angiofibromas and other TSC skin lesions.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Topical rapamycin treatment impedes tumor growth and improves survival. Average tumor growth (A) and survival curves (B) for indicated treatment groups.
Figure 2
Figure 2
Rapamycin whole blood levels after treatment with topical and IP rapamycin. A) Whole blood rapamycin levels from tumor bearing animals from indicated treatment groups. Rapamycin levels were measured 24 hours after the final dose of rapamycin. B) Whole blood rapamycin levels were measured in cohorts of control mice with no tumors. As indicated, levels were measured 24 hours after either one or three doses of topical rapamycin. In some groups, Elizabethan collars or bandages were used to prevent ingestion of rapamycin ointment. All animals had rapamycin levels >3 ng/ml. The slightly higher levels in the Elizabethan collar group suggests that ingestion is not a major issue. The lower levels in the bandage groups suggests that the bandage polymer can affect drug absorption. C) Whole blood rapamycin levels were also measured 48 hours after the final dose in tumor bearing animals. D) In three of the control, non-tumor bearing groups, rapamycin levels were measured at 48 hours following their final treatment to compare to tumor bearing animals.
Figure 3
Figure 3
Rapamycin levels in tumor samples after treatment with topical or IP rapamycin. Rapamycin levels in tumor homogenates from indicated treatment groups were measured 24 hours (A, C) and 48 hours (B, D) after the final dose of rapamycin. Panels C and D are enlarged versions of the boxed-in data in panels A and B respectively.
See this image and copyright information in PMC

References

    1. Crino PB, Nathanson KL, Henske EP. The tuberous sclerosis complex. N Engl J Med. 2006;355:1345–1356. doi: 10.1056/NEJMra055323. - DOI - PubMed
    1. Schwartz RA, Fernandez G, Kotulska K, Jozwiak S. Tuberous sclerosis complex: advances in diagnosis, genetics, and management. J Am Acad Dermatol. 2007;57:189–202. doi: 10.1016/j.jaad.2007.05.004. - DOI - PubMed
    1. Dabora SL, Jozwiak S, Franz DN, Roberts PS, Nieto A, Chung J, Choy YS, Reeve MP, Thiele E, Egelhoff JC, Kasprzyk-Obara J, Domanska-Pakiela D, Kwiatkowski DJ. Mutational Analysis in a Cohort of 224 Tuberous Sclerosis Patients Indicates Increased Severity of TSC2, Compared with TSC1, Disease in Multiple Organs. Am J Hum Genet. 2001;68:64–80. doi: 10.1086/316951. - DOI - PMC - PubMed
    1. Franz DN, Brody A, Meyer C, Leonard J, Chuck G, Dabora S, Sethuraman G, Colby TV, Kwiatkowski DJ, McCormack FX. Mutational and radiographic analysis of pulmonary disease consistent with lymphangioleiomyomatosis and micronodular pneumocyte hyperplasia in women with tuberous sclerosis. Am J Respir Crit Care Med. 2001;164:661–668. - PubMed
    1. Gomez MR, Sampson JR, Whittemore VH. The tuberous sclerosis complex. Third Ed. Oxford, England, Oxford University Press; 1999.

Publication types

MeSH terms