PI3K/AKT/mTOR signaling pathway: an important driver and therapeutic target in triple-negative breast cancer

IF 4 3区 医学 Q1 OBSTETRICS & GYNECOLOGY Breast Cancer Pub Date : 2024-04-17 DOI:10.1007/s12282-024-01567-5
Huan-ping Zhang, Rui-yuan Jiang, Jia-yu Zhu, Ke-na Sun, Yuan Huang, Huan-huan Zhou, Ya-bing Zheng, Xiao-jia Wang
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Abstract

Triple-negative breast cancer (TNBC) is a highly heterogeneous tumor lacking estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression. It has higher aggressiveness and metastasis than other subtypes, with limited effective therapeutic strategies, leading to a poor prognosis. The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) signaling pathway is prevalently over-activated in human cancers and contributes to breast cancer (BC) growth, survival, proliferation, and angiogenesis, which could be an interesting therapeutic target. This review summarizes the PI3K/AKT/mTOR signaling pathway activation mechanism in TNBC and discusses the relationship between its activation and various TNBC subtypes. We also report the latest clinical studies on kinase inhibitors related to this pathway for treating TNBC. Our review discusses the issues that need to be addressed in the clinical application of these inhibitors.

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PI3K/AKT/mTOR 信号通路:三阴性乳腺癌的重要驱动因素和治疗靶点
三阴性乳腺癌(TNBC)是一种缺乏雌激素受体(ER)、孕激素受体(PR)和人表皮生长因子受体 2(HER2)表达的高度异质性肿瘤。与其他亚型相比,它具有更高的侵袭性和转移性,有效的治疗策略有限,导致预后不良。磷酸肌酸3-激酶(PI3K)/蛋白激酶B(AKT)/雷帕霉素机械靶标(mTOR)信号通路在人类癌症中普遍过度激活,并导致乳腺癌(BC)的生长、存活、增殖和血管生成,这可能是一个有趣的治疗靶点。本综述总结了PI3K/AKT/mTOR信号通路在TNBC中的激活机制,并讨论了其激活与各种TNBC亚型之间的关系。我们还报告了与该通路相关的激酶抑制剂治疗 TNBC 的最新临床研究。我们的综述讨论了这些抑制剂在临床应用中需要解决的问题。
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来源期刊
Breast Cancer
Breast Cancer ONCOLOGY-OBSTETRICS & GYNECOLOGY
CiteScore
6.70
自引率
2.50%
发文量
105
审稿时长
6-12 weeks
期刊介绍: Breast Cancer, the official journal of the Japanese Breast Cancer Society, publishes articles that contribute to progress in the field, in basic or translational research and also in clinical research, seeking to develop a new focus and new perspectives for all who are concerned with breast cancer. The journal welcomes all original articles describing clinical and epidemiological studies and laboratory investigations regarding breast cancer and related diseases. The journal will consider five types of articles: editorials, review articles, original articles, case reports, and rapid communications. Although editorials and review articles will principally be solicited by the editors, they can also be submitted for peer review, as in the case of original articles. The journal provides the best of up-to-date information on breast cancer, presenting readers with high-impact, original work focusing on pivotal issues.
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