Safety of mTOR inhibitors in adult solid organ transplantation

Ventura‐Aguiar, Pedro; Campistol, Josep M.; Diekmann, Fritz

doi:10.1517/14740338.2016.1132698

Cited by 98 publications

(80 citation statements)

References 172 publications

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“…Perhaps most notably, mTOR inhibitors such as the rapamycin derivative everolimus have been used extensively to combat transplant rejection (50). Because chronic rejection responses have been linked to the induction of antibodies to graft-specific alloantigens (51), information is needed concerning the nature of the responsible antibody-secreting cells and how mTOR inhibitors and other drugs affect their function and lifespan.…”

Section: Discussionmentioning

confidence: 99%

mTOR has distinct functions in generating versus sustaining humoral immunity

Jones¹,

Gaudette²,

Wilmore³

et al. 2016

Journal of Clinical Investigation

139

135

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. multiple comparisons, the Kruskal-Wallis test was used with Dunn's multiple comparison test. For qRT-PCR studies, the Shapiro-Wilk test was used to confirm a normal distribution for the resulting data. In each case, P values less than 0.05 were considered significant. Study approval. All animal studies described herein were reviewed and approved by the University of Pennsylvania IACUC. Animals were bred and maintained in accordance with institutional guidelines for animal welfare.

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Section: Discussionmentioning

confidence: 99%

mTOR has distinct functions in generating versus sustaining humoral immunity

Jones¹,

Gaudette²,

Wilmore³

et al. 2016

Journal of Clinical Investigation

139

135

View full text Add to dashboard Cite

show abstract

“…7 13 In patients with growing SEGA, angiomyolipoma or LAM, treatment with systemic mTOR inhibitors, which address the underlying pathophysiology of the disease, might be indicated and is also likely to result in simultaneous improvement of skin lesions. [13][14][15][16] However, systemic mTOR inhibitors can contribute to surgical complications and delayed wound healing; [17][18][19] therefore, elective procedures (eg, cutaneous surgery, laser treatment) might best be avoided while on systemic therapy. In patients not receiving systemic treatment, topical mTOR inhibitors or surgical procedures may be indicated.…”

Section: Treatment Of Tsc-associated Cutaneous Disordersmentioning

confidence: 99%

Cutaneous manifestations of tuberous sclerosis complex and the paediatrician's role

Cardis

DeKlotz

2017

Arch Dis Child

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Tuberous sclerosis complex (TSC) is a multisystem genetic disorder stemming from unregulated activation of the mammalian target of rapamycin (mTOR) pathway, resulting in the growth of hamartomas in multiple organs. TSC-related skin lesions often develop early in life and can be disfiguring, emotionally distressful and even painful at times. Recognition of TSC-associated skin features by paediatricians can be a catalyst for facilitating early implementation of treatment strategies and establishing appropriate follow-up care. The range of potential treatment options for symptomatic or disfiguring TSC-associated skin lesions includes non-pharmacological (surgical excision, laser therapy) and pharmacological (eg, topical or systemic mTOR inhibitors) alternatives. In this review, we discuss the relevance of TSC-associated skin findings, highlight available treatment options, review guideline recommendations and emphasise the role of the primary care physician in the management of this complex disease.

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“…Initial concerns about an increase in hepatic artery thrombosis after liver transplantation now appear unfounded [99]. The long-term effects associated with mTOR inhibitors include an increased risk for dyslipidemia, cytopenias, proteinuria, and aphthous stomatitis, which are typically mild and can usually be managed effectively with close monitoring of trough levels and pharmacologic intervention [100, 101]. …”

Section: Balancing Risks and Benefitsmentioning

confidence: 99%

Everolimus and Malignancy after Solid Organ Transplantation: A Clinical Update

Holdaas

Simone

Zuckermann

2016

Journal of Transplantation

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Malignancy after solid organ transplantation remains a major cause of posttransplant mortality. The mammalian target of rapamycin (mTOR) inhibitor class of immunosuppressants exerts various antioncogenic effects, and the mTOR inhibitor everolimus is licensed for the treatment of several solid cancers. In kidney transplantation, evidence from registry studies indicates a lower rate of de novo malignancy under mTOR inhibition, with some potentially supportive data from randomized trials of everolimus. Case reports and small single-center series have suggested that switch to everolimus may be beneficial following diagnosis of posttransplant malignancy, particularly for Kaposi's sarcoma and nonmelanoma skin cancer, but prospective studies are lacking. A systematic review has shown mTOR inhibition to be associated with a significantly lower rate of hepatocellular carcinoma (HCC) recurrence versus standard calcineurin inhibitor therapy. One meta-analysis has concluded that patients with nontransplant HCC experience a low but significant survival benefit under everolimus monotherapy, so far unconfirmed in a transplant population. Data are limited in heart transplantation, although observational data and case reports have indicated that introduction of everolimus is helpful in reducing the recurrence of skin cancers. Overall, it can be concluded that, in certain settings, everolimus appears a promising option to lessen the toll of posttransplant malignancy.

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Safety of mTOR inhibitors in adult solid organ transplantation

Cited by 98 publications

References 172 publications

mTOR has distinct functions in generating versus sustaining humoral immunity

mTOR has distinct functions in generating versus sustaining humoral immunity

Cutaneous manifestations of tuberous sclerosis complex and the paediatrician's role

Everolimus and Malignancy after Solid Organ Transplantation: A Clinical Update

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