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靶向抗癌治疗后的潜在卵巢毒性和不孕风险。

Potential ovarian toxicity and infertility risk following targeted anti-cancer therapies.

机构信息

MRC Centre for Reproductive Health, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.

Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.

出版信息

Reprod Fertil. 2022 Jul 11;3(3):R147-R162. doi: 10.1530/RAF-22-0020. eCollection 2022 Jul 1.

Abstract

UNLABELLED

Unlike traditional chemotherapy agents which are generally cytotoxic to all cells, targeted anti-cancer therapies are designed to specifically target proliferation mechanisms in cancer cells but spare normal cells, resulting in high potency and reduced toxicity. There has therefore been a rapid increase in their development and use in clinical settings, including in curative-intent treatment regimens. However, the targets of some of these drugs including kinases, epigenetic regulatory proteins, DNA damage repair enzymes and proteasomes, have fundamental roles in governing normal ovarian physiology. Inhibiting their action could have significant consequences for ovarian function, with potentially long-lasting adverse effects which persist after cessation of treatment, but there is limited evidence of their effects on reproductive function. In this review, we will use literature that examines these pathways to infer the potential toxicity of targeted anti-cancer drugs on the ovary.

LAY SUMMARY

Compared to traditional chemotherapy agents, anti-cancer therapies are thought to be highly effective at targeting cancer cells but sparing normal cells, resulting in reduced drug side effects. However, many of processes within the cells that these drugs affect are also important for the ovary to work normally, so suppressing them in this way could have long-lasting implications for female fertility. This review examines the potential toxicity of anti-cancer therapies on the ovary.

摘要

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与通常对所有细胞都具有细胞毒性的传统化疗药物不同,靶向抗癌疗法旨在专门针对癌细胞的增殖机制,但不影响正常细胞,从而具有高效力和降低毒性。因此,它们在临床环境中的开发和使用迅速增加,包括在治愈性治疗方案中。然而,这些药物中的一些靶点,包括激酶、表观遗传调节蛋白、DNA 损伤修复酶和蛋白酶体,在调节正常卵巢生理中起着重要作用。抑制它们的作用可能对卵巢功能产生重大影响,并且在治疗停止后仍会持续存在潜在的长期不良影响,但它们对生殖功能的影响证据有限。在这篇综述中,我们将使用研究这些途径的文献来推断靶向抗癌药物对卵巢的潜在毒性。

概述

与传统化疗药物相比,抗癌疗法被认为在靶向癌细胞方面非常有效,但不影响正常细胞,从而降低了药物的副作用。然而,这些药物影响的细胞内许多过程对于卵巢正常运作也很重要,因此以这种方式抑制它们可能对女性生育能力产生持久的影响。这篇综述检查了抗癌疗法对卵巢的潜在毒性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18b2/9346327/511bbd97c130/RAF-22-0020fig1.jpg

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