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依维莫司在氟维司群加 CDK4/6 抑制剂治疗的乳腺癌患者来源异种移植模型中的抗肿瘤活性。

Antitumor Activity of Eribulin After Fulvestrant Plus CDK4/6 Inhibitor in Breast Cancer Patient-derived Xenograft Models.

机构信息

Tsukuba Research Laboratories, Eisai Co., Ltd., Ibaraki, Japan.

Oncodesign, Dijon, France.

出版信息

Anticancer Res. 2020 Dec;40(12):6699-6712. doi: 10.21873/anticanres.14693.

Abstract

BACKGROUND/AIM: There is no established standard chemotherapy after administration of the combination endocrine plus CDK4/6 inhibitor therapy for luminal-type breast cancer. We used patient-derived xenograft (PDX) models to determine the antitumor activity of eribulin and capecitabine after endocrine therapy plus CDK4/6 inhibitor.

MATERIALS AND METHODS

We examined the antitumor activity of fulvestrant, palbociclib, eribulin, and capecitabine in 4 luminal-type breast cancer PDX models (OD-BRE-0188, -0438, -0450, -0745). In OD-BRE-0438, we determined the antitumor activity of chemotherapy after fulvestrant-palbociclib treatment. We also performed immunohistochemical analysis to explore the effects of treatment on E-cadherin in tumor tissues.

RESULTS

Fulvestrant, fulvestrant-palbociclib and chemotherapy had antitumor activity in the 4 PDX models. In OD-BRE-0438 (the most resistant to fulvestrant-palbociclib), eribulin had superior antitumor activity to capecitabine after fulvestrant plus palbociclib. Only eribulin tended to increase E-cadherin expression.

CONCLUSION

Eribulin had superior antitumor activity to capecitabine after fulvestrant-palbociclib in the OD-BRE-0438 model.

摘要

背景/目的:激素受体阳性(HR+)、人表皮生长因子受体 2 阴性(HER2-)型乳腺癌接受内分泌联合 CDK4/6 抑制剂治疗后,尚未确立标准的化疗方案。本研究旨在使用患者来源的异种移植(PDX)模型,评估内分泌联合 CDK4/6 抑制剂治疗后,艾瑞布林和卡培他滨的抗肿瘤活性。

材料与方法

我们在 4 例 HR+/HER2-型乳腺癌 PDX 模型(OD-BRE-0188、-0438、-0450、-0745)中,检测氟维司群、哌柏西利、艾瑞布林和卡培他滨的抗肿瘤活性。在 OD-BRE-0438 模型中,我们评估了氟维司群-哌柏西利治疗后的化疗抗肿瘤活性,并进行了免疫组化分析以探讨治疗对肿瘤组织中 E-钙黏蛋白的影响。

结果

氟维司群、氟维司群-哌柏西利和化疗在 4 例 PDX 模型中均具有抗肿瘤活性。在氟维司群-哌柏西利治疗耐药性最强的 OD-BRE-0438 模型中,艾瑞布林的抗肿瘤活性优于卡培他滨。仅艾瑞布林有增加 E-钙黏蛋白表达的趋势。

结论

在 OD-BRE-0438 模型中,氟维司群-哌柏西利治疗后,艾瑞布林的抗肿瘤活性优于卡培他滨。

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