2005
DOI: 10.1093/annonc/mdi113
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Abstract: Rapamycin and its derivatives (CCI-779, RAD001 and AP23576) are immunosuppressor macrolides that block mTOR (mammalian target of rapamycin) functions and yield antiproliferative activity in a variety of malignancies. Molecular characterization of upstream and downstream mTOR signaling pathways is thought to allow a better selection of rapamycin-sensitive tumours. For instance, a loss of PTEN functions results in Akt phosphorylation, cell growth and proliferation; circumstances that can be blocked using rapamyc… Show more

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Cited by 563 publications
(426 citation statements)
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“…The results from a current clinical trial support the use of CCI-779 for mantle cell lymphoma intervention, likely in combination with other agents, such as antiangiogenic drugs or histone acetylase inhibitors [38] . Similar to CCI-779 (intravenous formulation), two other rapamycin analogs are RAD001 (or Everolimus, oral formulation) and AP23573 (intravenous formulation), both of which display a good safety profile with mild, dose-limiting toxicities compared with rapamycin [39] . These rapamycin derivatives are better therapeutic strategies against cancer.…”
Section: Rapamycin and Its Derivativesmentioning
confidence: 99%
“…The results from a current clinical trial support the use of CCI-779 for mantle cell lymphoma intervention, likely in combination with other agents, such as antiangiogenic drugs or histone acetylase inhibitors [38] . Similar to CCI-779 (intravenous formulation), two other rapamycin analogs are RAD001 (or Everolimus, oral formulation) and AP23573 (intravenous formulation), both of which display a good safety profile with mild, dose-limiting toxicities compared with rapamycin [39] . These rapamycin derivatives are better therapeutic strategies against cancer.…”
Section: Rapamycin and Its Derivativesmentioning
confidence: 99%
“…The mammalian target of rapamycin (mTOR) is a major downstream effector of Akt (Hay and Sonenberg, 2004) that is emerging as an important player in cancer and represents a major therapeutic target in a number of ongoing clinical trials for cancer (Vignot et al, 2005). However, rapamycin derivatives, which are used in these clinical trials to inhibit mTOR, are also activating Akt owing to release from a negative feedback loop normally operating by mTOR activation to restrict Akt activity.…”
Section: Mitochondrial Hexokinases and Cancermentioning
confidence: 99%
“…mTOR activates ribosomal p70S6K and eukaryotic initiation factor EIF-4E and therefore translation. Everolimus (RAD-001) is a potent derivative of rapamycin, which has been shown to inhibit activation of mTOR and block the downstream signaling cascade (21,22).…”
Section: Introductionmentioning
confidence: 99%