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Skin cancer in solid organ transplant recipients: are mTOR inhibitors a game changer?

机译:实体器官移植受者的皮肤癌:mTOR抑制剂是否会改变游戏规则?

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While immunosuppressive agents are necessary to prevent the rejection of transplanted organs, and are a great medical success story for protecting against early allograft loss, graft and patient survival over the long term are diminished by side effects from these same drugs. One striking long-term side effect is a high rate of skin cancer development. The skin cancers that develop in transplant recipients tend to be numerous, as well as particularly aggressive, and are therefore a major contributor to morbidity and mortality in transplant recipients. An apparent reason for the high incidence of skin cancer likely relates to suppression of immune surveillance mechanisms, but other more direct effects of certain immunosuppressive drugs are also bound to contribute to cancers of UV-exposed skin. However, over the past few years, evidence has emerged to suggest that one class of immunosuppressants, mammalian target of rapamycin (mTOR) inhibitors, could potentially inhibit skin tumour formation through a number of mechanisms that are still being studied intensively today. Therefore, in light of the high skin cancer incidence in transplant recipients, it follows that clinical trials have been conducted to determine if mTOR inhibitors can significantly reduce these post-transplant skin malignancies. Here, the problem of post-transplant skin cancer will be briefly reviewed, along with the possible mechanisms contributing to this problem, followed by an overview of the relevant clinical trial results using mTOR inhibitors.
机译:虽然免疫抑制剂对于防止移植器官的排斥是必要的,并且是防止早期同种异体移植丢失的重要医学成功案例,但这些药物的副作用却降低了移植物和患者的长期生存率。一项长期的显着副作用是皮肤癌的高发率。在移植接受者中发展的皮肤癌趋向于众多,并且特别是侵袭性的,因此是移植接受者的发病率和死亡率的主要贡献者。皮肤癌高发的一个明显原因可能与免疫监视机制的抑制有关,但是某些免疫抑制药物的其他更直接的作用也必然会导致紫外线暴露的皮肤癌。然而,在过去的几年中,已经出现证据表明一类免疫抑制剂,即雷帕霉素(mTOR)抑制剂的哺乳动物靶标,可以通过许多仍在深入研究的机制来抑制皮肤肿瘤的形成。因此,鉴于移植受体中皮肤癌的高发率,因此已经进行了临床试验以确定mTOR抑制剂是否可以显着降低这些移植后皮肤恶性肿瘤。在这里,将简要回顾移植后皮肤癌的问题,以及导致该问题的可能机制,然后概述使用mTOR抑制剂的相关临床试验结果。

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