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实体器官移植受者的皮肤癌:mTOR抑制剂会是一个改变局面的因素吗?

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

作者信息

Geissler Edward K

机构信息

Section of Experimental Surgery, Department of Surgery, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, Regensburg, 93053 Germany.

出版信息

Transplant Res. 2015 Jan 14;4:1. doi: 10.1186/s13737-014-0022-4. eCollection 2015.

Abstract

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.

摘要

虽然免疫抑制剂对于防止移植器官的排斥反应是必要的,并且在预防早期移植物丢失方面是一个巨大的医学成功案例,但这些药物的副作用会降低移植物和患者的长期存活率。一个显著的长期副作用是皮肤癌的高发率。移植受者中发生的皮肤癌往往数量众多,而且特别具有侵袭性,因此是移植受者发病和死亡的主要原因。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,但某些免疫抑制药物的其他更直接作用也必然会导致紫外线暴露皮肤的癌症。然而,在过去几年中,有证据表明一类免疫抑制剂,即雷帕霉素靶蛋白(mTOR)抑制剂,可能通过一些仍在深入研究的机制来抑制皮肤肿瘤的形成。因此,鉴于移植受者中皮肤癌的高发病率,已经开展了临床试验来确定mTOR抑制剂是否能显著减少这些移植后皮肤恶性肿瘤。在此,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,随后概述使用mTOR抑制剂的相关临床试验结果。

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