Cancer Therapy Drugs inhibiting the phosphoinositide-(3)-kinase (PI3K) signaling pathway are effective in a subset of breast cancer patients. Tumors become resistant to these drugs, however, and this transition is often accompanied by increased transcription of genes regulated by the estrogen receptor. A better understanding of the mechanism linking PI3K signaling and estrogen receptor activity could potentially suggest strategies to prevent drug resistance. Toska et al. found that PI3K inhibition activates a specific epigenetic regulator, the histone methyltransferase KMT2D. The protein modifications catalyzed by KMT2D create a more open chromatin state, which unleashes estrogen receptor–dependent transcription. Thus, combination therapies consisting of PI3K inhibitors and KMT2D inhibitors may be more effective than PI3K inhibitors alone. Science , this issue p. [1324][1] [1]: /lookup/doi/10.1126/science.aah6893

中文翻译：

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染色质状态决定药物反应

抑制磷酸肌醇-(3)-激酶 (PI3K) 信号通路的癌症治疗药物对一部分乳腺癌患者有效。然而，肿瘤对这些药物产生抗药性，并且这种转变通常伴随着受雌激素受体调节的基因转录的增加。更好地了解将 PI3K 信号传导和雌激素受体活性联系起来的机制可能会提出预防耐药性的策略。托斯卡等人。发现抑制 PI3K 会激活特定的表观遗传调节因子，即组蛋白甲基转移酶 KMT2D。由 KMT2D 催化的蛋白质修饰产生更开放的染色质状态，从而释放雌激素受体依赖性转录。因此，由 PI3K 抑制剂和 KMT2D 抑制剂组成的联合疗法可能比单独使用 PI3K 抑制剂更有效。科学，这个问题 p。[1324][1][1]：/lookup/doi/10.1126/science.aah6893