Toxicity spectrum of inhibitors of mammalian target of rapamycin in organ transplantation: etiology, pathogenesis and treatment

Abstract

Introduction: Control of the immune responses is critical for body homeostasis. Immunosuppressive strategies have been critical to this enterprise as they reveal molecular and cellular mechanisms of immune-mediated tissue destruction.

Areas covered: While exerting potent effects to blockade critical processes during cell maturation prior to division and effector functions, the novel drug class of mammalian target of rapamycin inhibitors (mTORi) consequently exert adverse reactions due to disruption of pleiotropic physiologic pathways. This review includes selected clinical and preclinical materials from the time of the author's own first-in-human experience in 1993 through to 2009. The goal of this contribution is to provide a foundation in basic biochemical processes to allow the reader to understand the pathophysiology of adverse clinical reactions.

Expert opinion: mTORi, as potent agents for clinical immunosuppression, inevitably, disrupt multiple cellular pathways as well as important vectors of host resistance. Judicious use of this pharmacologic class demands dedication to learning strategies of individualization for patient needs and reactions in the manner of clinicians previously committed on the introduction of calcineurin inhibitors 3 decades ago.

Keywords::

• intracellular activation pathway disruption
• mTOR
• mTOR inhibitors
• sirolimus

Notes

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