mTOR, cancer and transplantation.
One of the most clinically important molecular signalling networks to emerge over the past decade is the mammalian target of rapamycin (mTOR) pathway. mTOR, the protein kinase at the core of this intricate and continually evolving pathway, controls cellular growth and behavior, impacting vital processes from immune reactivity to cancer progression. As researchers, surgeons and physicians in the field of organ transplantation, we have acquired a keen interest in regulating mTOR activity, because this molecule is not only able to block IL-2 signalling in T cells, and thus alloimmune reactivity, it is a critical part of the cellular circuitry which is often constitutively activated in neoplastic cells, leading to the all-too-often occurrence of cancer. Since allograft rejection and the development of cancer lead most lists for causing excess morbidity and mortality in our organ transplant population, a thorough and current understanding of the mTOR pathway becomes essential. In this review, we endeavor to unravel the latest molecular developments in mTOR signalling and use this basic knowledge to generate perspectives on how pharmacologic mTOR intervention may form a balance to impact long-term antidonor immune responses and the development of malignancy in transplant recipients.
Geissler
Edward K
EK
Department for Surgery, University of Regensburg, Regensburg, Germany. edward.geissler@klinik.uni-regensburg.de
Schlitt
Hans J
HJ
Thomas
George
G
D000818:Animals; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006084:Graft Rejection; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D000076222:Mechanistic Target of Rapamycin Complex 1; D008954:Models, Biological; D046912:Multiprotein Complexes; D009369:Neoplasms / Q000150:complications* / Q000209:etiology* / Q000378:metabolism; D009389:Neovascularization, Pathologic; D016377:Organ Transplantation / Q000009:adverse effects*; D011494:Protein Kinases / Q000502:physiology*; D011506:Proteins; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases; D014157:Transcription Factors / Q000378:metabolism
C493245:CRTC2 protein, human; D007376:Interleukin-2; D046912:Multiprotein Complexes; D011506:Proteins; D014157:Transcription Factors; D011494:Protein Kinases; C546842:MTOR protein, human; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases