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针对磷酸肌醇3激酶/蛋白激酶B/雷帕霉素作用机制靶点通路治疗三阴性乳腺癌的策略

Treatment strategies targeting the phosphoinositide 3-kinase/protein kinase B/mechanistic target of rapamycin pathway against triple-negative breast cancer.

作者信息

Ni Chun-Xiao, Xu Jia-Ju, Pang Yu, Xu Jia-Ju

机构信息

Department of Minimally Invasive Oncology, Tai'an Central Hospital Affiliated to Qingdao University, Tai'an 271000, Shandong Province, China.

Department of Pediatrics, Yantai Yuhuangding Hospital Affiliated to Qingdao University, Yantai 264000, Shandong Province, China.

出版信息

World J Clin Oncol. 2025 May 24;16(5):104623. doi: 10.5306/wjco.v16.i5.104623.

DOI:10.5306/wjco.v16.i5.104623
PMID:40503407
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12149821/
Abstract

Triple negative breast cancer (TNBC) is an exceptionally aggressive subtype of breast cancer with a poor prognosis. TNBC patients have limited treatment options beyond conventional chemotherapy, and they face significant challenges associated with disease recurrence and resistance to chemotherapy. The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) signaling pathway plays a pivotal role in cell proliferation, growth, metabolism, and survival. Its aberrant activation is closely linked to the development and progression of TNBC, as well as treatment response and drug resistance. Currently, numerous targeted drugs specifically inhibiting this signaling pathway are being developed and undergoing clinical trials. These include inhibitors targeting PI3K, AKT, or mTOR individually, as well as dual-target or multi-target inhibitors simultaneously targeting different components of this pathway. Encouragingly, some inhibitors have demonstrated promising potential in clinical trials. This review delves into the therapeutic potential of the PI3K/AKT/mTOR signaling pathway for TNBC and explores prospects for drug discovery.

摘要

三阴性乳腺癌(TNBC)是一种侵袭性极强的乳腺癌亚型,预后较差。TNBC患者除了传统化疗外,治疗选择有限,且面临疾病复发和化疗耐药相关的重大挑战。磷酸肌醇3-激酶(PI3K)/蛋白激酶B(AKT)/雷帕霉素靶蛋白(mTOR)信号通路在细胞增殖、生长、代谢和存活中起关键作用。其异常激活与TNBC的发生发展、治疗反应及耐药密切相关。目前,许多特异性抑制该信号通路的靶向药物正在研发并进行临床试验。这些药物包括单独靶向PI3K、AKT或mTOR的抑制剂,以及同时靶向该通路不同组分的双靶点或多靶点抑制剂。令人鼓舞的是,一些抑制剂在临床试验中已显示出有前景的潜力。本综述深入探讨了PI3K/AKT/mTOR信号通路对TNBC的治疗潜力,并探索药物研发前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3363/12149821/6f5f16181db0/104623-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3363/12149821/e023a5e856f6/104623-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3363/12149821/6f5f16181db0/104623-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3363/12149821/e023a5e856f6/104623-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3363/12149821/6f5f16181db0/104623-g002.jpg

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本文引用的文献

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Int J Mol Sci. 2024 Dec 17;25(24):13518. doi: 10.3390/ijms252413518.
2
Evaluation of lncRNAs as Potential Biomarkers for Diagnosis of Metastatic Triple-Negative Breast Cancer through Bioinformatics and Machine Learning.通过生物信息学和机器学习评估长链非编码RNA作为转移性三阴性乳腺癌诊断潜在生物标志物的研究
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Inavolisib-Based Therapy in -Mutated Advanced Breast Cancer.
伊沙匹隆为基础的疗法治疗 - 突变型晚期乳腺癌。
N Engl J Med. 2024 Oct 31;391(17):1584-1596. doi: 10.1056/NEJMoa2404625.
4
Osteopontin is a therapeutic target that drives breast cancer recurrence.骨桥蛋白是一种促进乳腺癌复发的治疗靶点。
Nat Commun. 2024 Oct 24;15(1):9174. doi: 10.1038/s41467-024-53023-9.
5
NRF3 suppresses the malignant progression of TNBC by promoting M1 polarization of macrophages via ROS/HMGB1 axis.NRF3 通过 ROS/HMGB1 轴促进巨噬细胞 M1 极化来抑制三阴性乳腺癌的恶性进展。
Cancer Biol Ther. 2024 Dec 31;25(1):2416221. doi: 10.1080/15384047.2024.2416221. Epub 2024 Oct 23.
6
Overexpression of Osteopontin-a and Osteopontin-c Splice Variants Are Worse Prognostic Features in Colorectal Cancer.骨桥蛋白-a和骨桥蛋白-c剪接变体的过表达是结直肠癌预后较差的特征。
Diagnostics (Basel). 2024 Sep 24;14(19):2108. doi: 10.3390/diagnostics14192108.
7
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