Ni CX, Xu JJ, Pang Y, Xu JJ. 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; 16(5): 104623 [DOI: 10.5306/wjco.v16.i5.104623]
Corresponding Author of This Article
Jia-Ju Xu, MD, Department of Medical Oncology, Tai’an Central Hospital Affiliated to Qingdao University, No. 29 Longtan Road, Taishan District, Tai’an 271000, Shandong Province, China. jiajuxu1101@163.com
Research Domain of This Article
Oncology
Article-Type of This Article
Review
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Clin Oncol. May 24, 2025; 16(5): 104623 Published online May 24, 2025. doi: 10.5306/wjco.v16.i5.104623
Treatment strategies targeting the phosphoinositide 3-kinase/protein kinase B/mechanistic target of rapamycin pathway against triple-negative breast cancer
Chun-Xiao Ni, Jia-Ju Xu, Yu Pang, Jia-Ju Xu
Chun-Xiao Ni, Department of Minimally Invasive Oncology, Tai’an Central Hospital Affiliated to Qingdao University, Tai’an 271000, Shandong Province, China
Jia-Ju Xu, Department of Pediatrics, Yantai Yuhuangding Hospital Affiliated to Qingdao University, Yantai 264000, Shandong Province, China
Yu Pang, Department of Pathology, Tai’an Central Hospital Affiliated to Qingdao University, Tai’an 271000, Shandong Province, China
Jia-Ju Xu, Department of Medical Oncology, Tai’an Central Hospital Affiliated to Qingdao University, Tai’an 271000, Shandong Province, China
Co-first authors: Chun-Xiao Ni and Jia-Ju Xu.
Author contributions: Ni CX and Xu JJ are co-first authors, the two authors made equal contributions to this work and played essential roles in the critical stages of research design, data collection and analysis, and manuscript preparation. Ni CX drafted the initial manuscript; Xu JJ collected, analyzed the data, and contributed to the discussion of results; Pang Y assisted in data collection and analysis; Xu JJ conceived and designed the review and critically revised the manuscript for important intellectual content.
Supported by the Scientific Research Fund of Tai’an Science and Technology Agency, No. 2019NS180.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jia-Ju Xu, MD, Department of Medical Oncology, Tai’an Central Hospital Affiliated to Qingdao University, No. 29 Longtan Road, Taishan District, Tai’an 271000, Shandong Province, China. jiajuxu1101@163.com
Received: December 31, 2024 Revised: February 25, 2025 Accepted: March 25, 2025 Published online: May 24, 2025 Processing time: 144 Days and 14.7 Hours
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.
Core Tip: Triple-negative breast cancer is an aggressive subtype of breast cancer with a poor prognosis. The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) signaling pathway regulates cell proliferation, growth, metabolism, and survival. This review analyzes biomarkers associated with this pathway in triple-negative breast cancer, including proteins, mRNA, non-coding RNA, and transcription factors. Furthermore, it systematically examines key natural products targeting the pathway, such as flavonoids, terpenoids, and alkaloids. Finally, it provides a comprehensive overview of inhibitors used to target the PI3K/AKT/mTOR pathway, including PI3K, mTOR, dual PI3K/mTOR, and AKT inhibitors.
