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癌症研究的诊断和治疗疗法的进展使医生能够更早地捕获和治疗癌症，从而在许多情况下可以更好地预测。但是，这也意味着在传统上被视为关键生殖年份中，正在为癌症提供更多的妇女。尽管药物的临床试验检查了对患者的副作用，但他们通常不考虑对该患者未来后代的影响。With the evolution of genetically-based approaches to cancer treatments, and specifically epigenetically-based therapeutics, changes being introduced into a patient’s epigenome by the targeted treatment drugs could have lasting impacts on the germline genome that is passed to the patient’s offspring, with potentially unintentional, negative effects. Given that female mammals are born with a set number of eggs (oocytes) and more females of reproductive age are being treated for cancers, there is clearly a need to more fully understand the possible ramifications of these new therapies for women who might wish to have children post-treatment.

在最近发表的一项研究中Clinical Epigenetics,研究人员检查了新德的影响veloped epigenetic drug Tazemetostat (currently in clinical trials; it works by inhibiting the target enzyme Enhancer of Zeste 2 (EZH2)) on mice of reproductive age. Because EZH1 and EZH2 are implicated in gain of function mutations and overexpression in a range of tumors, it was selected as target for epigenetic therapy: i.e., inhibit expression of this enzyme, inhibit expression of the gene that might lead to mutation or proliferation of cancer cells in tumors. However, while the inhibition of EZH1/2 might be a targeted treatment for cancer and other diseases, in this study the inhibition of EZH1/2 was shown to severely deplete H3K27me3, which is necessary for growing oocytes in female mice. As a result, both oocyte growth and fetal oocyte development were both negatively impacted in female mice treated with Tazemetostat.

更令人震惊的是，研究人员发现，一旦H3K27me3耗尽，即使在终止治疗后也没有恢复。耗竭造成的损害持续，导致母亲的基因组和其卵母细胞的H3K27me3蛋白损失（显然影响种系）。尽管这项研究是在实验室小鼠中进行的，但研究人员强烈提倡在人类女性中可以看到这些相同的影响，并要求在临床试验中进行更广泛的研究，以检查这些其他可能的后果。

鉴于这项研究的结果，很明显，需要进行更多的研究，这些研究在开发和测试基于表观遗传的药物时检查了对生育能力和未来后代的潜在影响，这些药物可能从根本上改变了与生育有关的基因的功能。和生殖成功。Prokopuk，Hogg和Western的研究是一个警示性的故事，提醒我们，有时在针对癌症的战争中可能会有不可预见的价格，但是知道我们现在对遗传学和表观遗传学的了解，以及我们所有的一切都继续学习 - 研究者可以对自己的了解，以了解给定疗法的所有潜在副作用，以进一步为某些患者乃至特定患者的人群进一步完善它：真实的精确药物。