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6 Challenges for clinical use of IGF-1R-silencing agents 6.1 Toxicity of IGF-1R antagonists Clinical trials of a large number IGF-1/2, IGF-1R, IRS-1, PI3K and mTOR antagonists have been abandoned due to limited anti-cancer activity, or to the toxicity of these agents (41, 53), further supporting the need to continue studies on LL6 and other molecules that are well tolerated in mice and effective at doses that are not toxic to normal cells (54)

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Histological assessment and scoring were performed by a pathologist blinded to the study conditions

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