Table 1.

Summary of animal studies supporting the role of rapamycin-mediated inhibition of mTOR in cancer therapy/prevention

Cancer typeDescription of effectsReferences
SkinReduction in tumor numbers, tumor size, and progression of benign lesions to SCCs in UVB-induced SKH-1 hairless, DMBA–TPA 2-stage and cyclosporine A–mediated carcinogenesis in various murine models22,26, 38–41
Head and neckReduction in the oral carcinogen-specific mouse model, human xenograft, and oral-specific Kras/p53 two-hit carcinogenesis murine models22, 42–44
Gastrointestinal (liver, intestine, stomach, and pancreas)Inhibition of hepatocellular carcinoma in xenograft and orthotopic murine models; reduction in intestinal polyp formation and mortality in ApcΔ716 engineered mice; inhibition of gastric cancer in xenograft immune deficient mouse models; mimicked the anticancer effects of calorie restriction in a murine model of pancreatic cancer28, 36, 45–47
KidneyInhibition of tumor growth in A/J Tsc2+/− mice and xenograft models48, 49
BreastInhibition of tumor growth of premalignant and malignant lesions in ductal carcinoma in situ and Erb2-dependent transgenic breast cancer mouse models50, 51
ProstateDiminution of prostate adenocarcinoma in Pten+/− and Pten+/−/Tsc2+/−mice.52
BladderPrevention of invasive bladder cancer in a murine model carrying bladder epithelium-specific deletion of p53 and Pten.53
RhabdomyosarcomaLack of published studies in murine models, however, a clear benefit of combinatorial chemotherapy in humans54
LungInhibition of benzo(a)pyrene-, tobacco carcinogen (NNK)-induced lung tumorigenesis in A/J as well as in Tsc1/Kras double-mutant mice23, 55, 56
AnalRapamycin slowed the growth of anal cancer both in a murine model and in humans57
UterineEker rat model of uterine leiomyomata faithfully recapitulates the human transcriptional profile of this tumor. In this model, mTOR activation (followed by IRS-1 phosphorylation) occurs early, or in endometrial hyperplasia, and the rapamycin analogue WAY-129327 significantly decreased hyperplasia, proliferation, and tumor incidence, multiplicity, and size58

Abbreviations: DMBA, 7,12-dimethylbenz[α]anthracene; NNK, nicotine-derived nitrosamine ketone; IRS-1, insulin-receptor substrate 1.