Bone-Induced Her2 Promotes Secondary Metastasis in HR+/Her2- Breast Cancer.

IF 29.7 1区医学 Q1 ONCOLOGY

Cancer discovery Pub Date : 2025-01-21 DOI:10.1158/2159-8290.cd-23-0543

Rahat Alam,Anna Reva,David G Edwards,Bree M Lege,Laura S Munoz-Arcos,Carolina Reduzzi,Swarnima Singh,Xiaoxin Hao,Yi-Hsuan Wu,Zeru Tian,Laura M Natalee,Gargi Damle,Deniz Demircioglu,Yixian Wang,Ling Wu,Elisabetta Molteni,Dan Hasson,Bora Lim,Zbigniew Gugala,Jerry E Chipuk,Julie E Lang,Joseph A Sparano,Chonghui Cheng,Massimo Cristofanilli,Han Xiao,Xiang H-F Zhang,Igor L Bado

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引用次数: 0

Abstract

Bone metastases can disseminate to secondary sites and promote breast cancer progression creating additional clinical challenges. The mechanisms contributing to secondary metastasis are barely understood. Here, we evaluate the prediction power of Her2-expressing (Her2E) circulating tumor cells (CTCs) after analyzing over 13,000 CTCs from a cohort of 137 metastatic breast cancer (MBC) patients with initial HR+/Her2- status and employ preclinical models of bone metastasis (BM) to validate the role of Her2E CTCs in multi-organ metastases. While Her2 expression was higher in patients with bone metastasis, experimental analyses revealed that Her2E CTCs derived from bone lesions were more dependent on Her2 activity and more susceptible to anti-Her2 therapy. Targeting the bone-mediated Her2 induction reduces CTC detection and abrogates secondary metastasis from bone. Overall, we elucidate that Her2E CTCs can serve as a non-invasive biomarker for BM formation with high therapeutic benefit for HR+ MBC patients.

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骨诱导的Her2促进HR+/Her2-乳腺癌的继发性转移

骨转移可以扩散到继发部位，促进乳腺癌的进展，带来额外的临床挑战。导致继发性转移的机制尚不清楚。在这里，我们分析了137例初始HR+/Her2-状态的转移性乳腺癌（MBC）患者的13000多个循环肿瘤细胞（CTCs），评估了Her2表达（Her2E）循环肿瘤细胞（CTCs）的预测能力，并采用骨转移（BM）的临床前模型来验证Her2E CTCs在多器官转移中的作用。虽然Her2在骨转移患者中表达较高，但实验分析显示，骨病变产生的Her2E ctc更依赖Her2活性，更容易接受抗Her2治疗。靶向骨介导的Her2诱导可减少CTC检测并消除骨的继发性转移。总的来说，我们阐明Her2E ctc可以作为HR+ MBC患者BM形成的非侵入性生物标志物，具有很高的治疗效益。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer discovery ONCOLOGY-

CiteScore

22.90

自引率

1.40%

发文量

838

审稿时长

6-12 weeks

期刊介绍： Cancer Discovery publishes high-impact, peer-reviewed articles detailing significant advances in both research and clinical trials. Serving as a premier cancer information resource, the journal also features Review Articles, Perspectives, Commentaries, News stories, and Research Watch summaries to keep readers abreast of the latest findings in the field. Covering a wide range of topics, from laboratory research to clinical trials and epidemiologic studies, Cancer Discovery spans the entire spectrum of cancer research and medicine.