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2019年乳腺癌和卵巢癌的转化研究亮点——免疫疗法、DNA修复、PI3K抑制及CDK4/6疗法

Translational Highlights in Breast and Ovarian Cancer 2019 - Immunotherapy, DNA Repair, PI3K Inhibition and CDK4/6 Therapy.

作者信息

Hartkopf Andreas D, Müller Volkmar, Wöckel Achim, Lux Michael P, Janni Wolfgang, Ettl Johannes, Belleville Erik, Schütz Florian, Fasching Peter A, Kolberg Hans-Christian, Welslau Manfred, Overkamp Friedrich, Taran Florin-Andrei, Brucker Sara Y, Wallwiener Markus, Tesch Hans, Fehm Tanja N, Schneeweiss Andreas, Lüftner Diana

机构信息

Department of Obstetrics and Gynecology, University of Tübingen, Tübingen, Germany.

Department of Gynecology, Hamburg-Eppendorf University Medical Center, Hamburg, Germany.

出版信息

Geburtshilfe Frauenheilkd. 2019 Dec;79(12):1309-1319. doi: 10.1055/a-1039-4458. Epub 2019 Dec 11.

Abstract

In the near future, important translational questions of clinical relevance will be adressed by studies currently in progress. On the one hand, the role of PD-L1 expression must be further understood, after it was found to be relevant in the use of atezolizumab in first-line therapy of patients with metastatic triple-negative breast cancer (TNBC). No association between efficacy and PD-L1 expression was found in a neoadjuvant study that included pembrolizumab in TNBC. The pathological complete response rate (pCR) was higher in both patient groups with and without PD-L1 expression when pembrolizumab was added to chemotherapy. Another future question is the identification of further patient groups in which efficacy of PARP inhibitors is seen, which are licensed for the germline mutation. These include, for example, patients with mutations in other genes, which are involved in homologous recombination, or patients with tumours that show an abnormality in global tests of homologous recombination deficiencies (HRD tests). The question of whether a PARP inhibitor can be given and with which chemotherapy combination partners is currently being investigated in both breast and ovarian cancer. While the data on improved overall survival are being consolidated for the CDK4/6 inhibitors, knowledge of molecular changes during the therapy and during progression on the therapy is growing. Both the accumulation of PI3K mutations and also PTEN changes might play a part in planning subsequent therapies. This review article summarises these recent developments in breast cancer and in part also in ovarian cancer.

摘要

在不久的将来,目前正在进行的研究将解决具有临床相关性的重要转化问题。一方面,在发现程序性死亡受体配体1(PD-L1)表达与阿替利珠单抗用于转移性三阴性乳腺癌(TNBC)患者的一线治疗相关后,其作用必须得到进一步了解。在一项新辅助研究中,未发现TNBC患者使用帕博利珠单抗时疗效与PD-L1表达之间存在关联。当化疗中加入帕博利珠单抗时,无论有无PD-L1表达,两组患者的病理完全缓解率(pCR)均较高。另一个未来的问题是确定其他能观察到聚(ADP-核糖)聚合酶(PARP)抑制剂疗效的患者群体,这些抑制剂已获批用于种系突变。例如,这些群体包括其他参与同源重组的基因突变患者,或在同源重组缺陷整体检测(HRD检测)中显示异常的肿瘤患者。目前,乳腺癌和卵巢癌都在研究是否可以使用PARP抑制剂以及与哪些化疗联合用药。虽然关于细胞周期蛋白依赖性激酶4/6(CDK4/6)抑制剂改善总生存期的数据正在汇总,但治疗期间和疾病进展过程中的分子变化知识也在不断增加。磷脂酰肌醇-3-激酶(PI3K)突变的积累以及第10号染色体同源丢失性磷酸酶-张力蛋白(PTEN)的变化可能在后续治疗方案的制定中发挥作用。这篇综述文章总结了乳腺癌以及部分卵巢癌的这些最新进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/50e9/6924326/3172d6cc3b1c/10-1055-a-1039-4458-igf01.jpg

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