mTOR inhibitor/proliferation signal inhibitors: entering or leaving the field?

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Rostaing L, Kamar N

mTOR inhibitor/proliferation signal inhibitors: entering or leaving the field?

J Nephrol. 2010 Mar-Apr;23(2):133-42.

PubMed ID

20155724 [ View in PubMed

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Abstract

BACKGROUND: The mammalian target of rapamycin (mTOR) is a highly conserved serine/threonine kinase that controls cell growth and metabolism in response to nutrients, growth factors, cellular energy and stress, and has pleiotropic effects. Its blockade, by mTOR inhibitors (mTOR-Is), such as sirolimus or everolimus, leads to antiproliferative effects. METHODS: We have reviewed the major studies that deal with the utilization of mTOR-Is after kidney transplant and the outcomes. RESULTS: Calcineurin-inhibitor (CNI) avoidance, under the umbrella of sirolimus-based immunosuppression in de novo kidney-transplant (KT) patients, is associated with worse results compared with those observed in patients receiving CNI-based immunosuppression. Conversely, using mTOR-Is in the context of CNI minimization and CNI-free protocols is safe and efficient when used after 3 months post-transplant. If cyclosporin A (CsA) is used in combination with mTOR-I, considerable dose reduction of both drugs is required. A better choice may be withdrawal of CsA from this combination after 3-12 months. Later withdrawal or conversion to an mTOR-I may not be beneficial. Kidney transplant recipients given mTOR-Is have reduced incidence of de novo posttransplant malignancies. Posttransplant Kaposi's sarcoma and nonmelanotic skin malignancies frequently undergo remission/regression after conversion to mTOR-I immunosuppression. The associated side effects of mTOR-Is are numerous and may lead to significant drug cessation. CONCLUSION: mTOR-Is could be more widely used in kidney transplant patients due to reduced nephrotoxicity and de novo cancer compared with CNIs.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Everolimus	Serine/threonine-protein kinase mTOR	Protein	Humans	Yes	Inhibitor	Details