MTOR and neoplasm: In preclinical studies, cells exposed to mTOR inhibitors demonstrated increased expression of the phosphorylated AKT, which in turn activates downstream signalling through alternative pathways, including forkhead transcription factor and glycogen synthase kinase-3, that can bypass the mTOR complex.10,11 Immunomodulatory agents such as lenalidomide can overcome cellular tolerance of mTOR inhibition through putative mechanisms such as enhanced anti-tumour immunity and induction of E3 ligase.