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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

相似文献

[1]
Treatment strategies targeting the phosphoinositide 3-kinase/protein kinase B/mechanistic target of rapamycin pathway against triple-negative breast cancer.

World J Clin Oncol. 2025-5-24

[2]
Targeting the PI3K/AKT/mTOR pathway in triple-negative breast cancer: a review.

Breast Cancer Res Treat. 2018-2-7

[3]
PI3K/AKT/mTOR signaling pathway: an important driver and therapeutic target in triple-negative breast cancer.

Breast Cancer. 2024-7

[4]
Perspectives on Triple-Negative Breast Cancer: Current Treatment Strategies, Unmet Needs, and Potential Targets for Future Therapies.

Cancers (Basel). 2020-8-24

[5]
Long noncoding RNA-mediated activation of PROTOR1/PRR5-AKT signaling shunt downstream of PI3K in triple-negative breast cancer.

Proc Natl Acad Sci U S A. 2022-10-25

[6]
Targeting the PI3K/AKT/mTOR Pathway for the Treatment of Mesenchymal Triple-Negative Breast Cancer: Evidence From a Phase 1 Trial of mTOR Inhibition in Combination With Liposomal Doxorubicin and Bevacizumab.

JAMA Oncol. 2017-4-1

[7]
Antiplatelet drug ticagrelor suppresses triple negative breast cancer metastasis by targeting PI3K.

Biochem Pharmacol. 2024-8

[8]
Therapeutic Potential of Autophagy in Glioblastoma Treatment With Phosphoinositide 3-Kinase/Protein Kinase B/Mammalian Target of Rapamycin Signaling Pathway Inhibitors.

Front Oncol. 2020-10-2

[9]
The PI3K/mTOR dual inhibitor NVP-BEZ235 stimulates mutant p53 degradation to exert anti-tumor effects on triple-negative breast cancer cells.

FEBS Open Bio. 2020-4

[10]
Myricetin-induced apoptosis in triple-negative breast cancer cells through inhibition of the PI3K/Akt/mTOR pathway.

Med Oncol. 2022-10-8

本文引用的文献

[1]
Latest Therapeutical Approaches for Triple-Negative Breast Cancer: From Preclinical to Clinical Research.

Int J Mol Sci. 2024-12-17

[2]
Evaluation of lncRNAs as Potential Biomarkers for Diagnosis of Metastatic Triple-Negative Breast Cancer through Bioinformatics and Machine Learning.

Iran J Biotechnol. 2024-7-1

[3]
Inavolisib-Based Therapy in -Mutated Advanced Breast Cancer.

N Engl J Med. 2024-10-31

[4]
Osteopontin is a therapeutic target that drives breast cancer recurrence.

Nat Commun. 2024-10-24

[5]
NRF3 suppresses the malignant progression of TNBC by promoting M1 polarization of macrophages via ROS/HMGB1 axis.

Cancer Biol Ther. 2024-12-31

[6]
Overexpression of Osteopontin-a and Osteopontin-c Splice Variants Are Worse Prognostic Features in Colorectal Cancer.

Diagnostics (Basel). 2024-9-24

[7]
PI3K/AKT/mTOR inhibitors for the management of triple-negative breast cancer.

Med Oncol. 2024-10-14

[8]
Anticancer Drug Discovery from Natural Compounds Targeting PI3K/AKT/mTOR Signaling Pathway.

Curr Med Chem. 2024-10-10

[9]
Breast cancer statistics 2024.

CA Cancer J Clin. 2024

[10]
ACTL8 Promotes the Progression of Gastric Cancer Through PI3K/AKT/mTOR Signaling Pathway.

Dig Dis Sci. 2024-10

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