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Comment
. 2011 Jul;4(7):957-61.
doi: 10.1158/1940-6207.CAPR-11-0266.

Rapamycin and mTORC1 inhibition in the mouse: skin cancer prevention

Mohammad Athar  1 , Levy Kopelovich
Affiliations
Comment

Rapamycin and mTORC1 inhibition in the mouse: skin cancer prevention

Mohammad Athar et al. Cancer Prev Res (Phila). 2011 Jul.

Abstract

Therapeutic and preventive effects of rapamycin include reduced risk of nonmelanoma skin cancer (NMSC). In this issue of the journal (beginning on page 1011), Checkley and colleagues report that rapamycin inhibits mTOR complex 1 in murine epidermis, thereby inhibiting tumor promotion mediated by tetradecanoyl phorbol-13 acetate in association with a strong anti-inflammatory effect. Rapamycin is an immunosuppressive drug for preventing graft rejection in organ transplant recipients and reduces the risk of NMSC and Kaposi's sarcoma in this population, albeit by mechanisms distinct from immunosuppression. Important future directions include identifying molecular predictors of rapamycin/rapalog sensitivity or resistance (potentially, for example, PI3K pathway alterations and KRAS mutations) and combined non-rapalog, mTOR-targeting approaches, all of which should increase efficacy and minimize toxicity.

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Conflict of interest statement

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were reported.

Figures

Figure 1
Figure 1
mTOR signaling cascade in the pathogenesis and prevention of skin cancer. The skin tumor promoter TPA induces mTORC1 activity, which in turn enhances the AKT --dependent cell-survival signaling pathway. TPA-mediated mTORC1 activation augments epidermal hyperplasia and dermal inflammation. Rapamycin inhibits TPA-mediated inflammation and tumor promotion by inhibiting mTORC1 activity. MDM2, murine double minute, pTEN, phosphatase and tensin homolog.
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