1. Nat. Rev. Clin. Oncol. doi:10.1038/nrclinonc.2015.186
Figure 1 Effects of mTOR inhibitors on allograft survival and tumour development
Figure 1 | Effects of mTOR inhibitors on allograft survival and tumour development. mTOR complex 1 (mTORC1) has a central role in integrating growth factor and other cellular signals with cellular energy and nutrient status. This signalling pathway is fundamental to the function of normal, as well as aberrant cells, thus it is not surprising that inhibiting mTORC1 with rapamycin (or rapamycin derivatives) can have profound effects on many processes, in a wide variety of cell types. mTORC1 signalling affects cell growth and proliferation, and, crucially, the differentiation and development of cellular components of the immune system are critically dependent on its activity. The intricate nature of this balance of effects on different systems is clearly demonstrated in the situation where an allograft and tumour coexist. Therapeutic mTOR inhibition can both inhibit the immune reaction to a transplanted organ, and at the same time, promote other processes that inhibit tumour growth (that is, antiangiogenesis), including the stimulation of memory CD8+ T-cell responses against the tumour. The complexity of this situation requires that rigorous clinical trials be conducted in the transplantation setting to determine whether mTOR inhibitors can actually benefit allograft recipients who are at a high risk of post-transplant malignancy (see also Box 5). Abbreviations: mTOR, mammalian target of rapamycin; mTORC1, mammalian target of rapamycin complex 1.
Geissler, E. K. (2015) Post-transplantation malignancies: here today, gone tomorrow?
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