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Review
. 2013 Dec 1;2(12):e26961.
doi: 10.4161/onci.26961. Epub 2013 Nov 6.

Immunosuppressants in cancer prevention and therapy

Mikhail V Blagosklonny  1
Affiliations
Review

Immunosuppressants in cancer prevention and therapy

Mikhail V Blagosklonny. Oncoimmunology. .

Abstract

Rapalogs such as rapamycin (sirolimus), everolimus, temserolimus, and deforolimus are indicated for the treatment of some malignancies. Rapamycin is the most effective cancer-preventive agent currently known, at least in mice, dramatically delaying carcinogenesis in both normal and cancer-prone murine strains. In addition, rapamycin and everolimus decrease the risk of cancer in patients receiving these drugs in the context of immunosuppressive regimens. In general, the main concern about the use of immunosuppressants in humans is an increased risk of cancer. Given that rapalogs are useful in cancer prevention and therapy, should they be viewed as immunosuppressants or immunostimulators? Or should we reconsider the role of immunity in cancer altogether? In addition to its anti-viral, anti-inflammatory, anti-angiogenic and anti-proliferative effects, rapamycin operates as a gerosuppressant, meaning that it inhibits the cellular conversion to a senescent state (the so-called geroconversion), a fundamental process involved in aging and age-related pathologies including cancer.

Keywords: cancer; geroconversion; immunosuppression; inflammation; mTOR; rapalog; rapamycin; senescence.

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Figures

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Figure 1. The mTOR pathway is involved in both cancer and senescence. Growth factors, cytokines, insulin, nutrients, and oncoproteins activate the phosphoinositide-3-kinase/mammalian target of rapamycin (PI3K/mTOR) signaling pathway, which promotes cellular growth and cell cycle progression. Mutations that results in constitutive activation of the mTOR pathway are involved in oncogenic transformation when intrinsic controls on cell cycle progression are disabled. Conversely, when mTOR is activated and the cell cycle is arrested, cells enter a senescent state. Rapamycin and other rapalogs (e.g., everolimus) inhibit the mTOR complex 1 (mTORC1) and suppress such a geroconversion.
See this image and copyright information in PMC

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