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This effect is enhanced when combined with the mTOR inhibitor temsirolimus.43 Importantly, loss-of-function mutations in the gene encoding the tumor suppressor Von Hippel-Lindau (VHL) are commonly observed in RCC.44 These mutations have been associated with increased activation of renal IGF-1 signaling and elevated IGF1R expression, resulting in a more aggressive tumor phenotype compared to RCC with wild-type VHL