The efficacy and safety of PI3K and AKT inhibitors for patients with cancer: A systematic review and network meta-analysis.

Autor:	Zhang Y; Teaching hospital of Shenyang Pharmaceutical University, General Hospital of Northern Theater Command, 100016, Shenyang city, Liaoning province, PR China; Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang city, Liaoning province, PR China. Electronic address: zhangyingshi@syphu.edu.cn., Xu X; Teaching hospital of Shenyang Pharmaceutical University, General Hospital of Northern Theater Command, 100016, Shenyang city, Liaoning province, PR China; Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang city, Liaoning province, PR China. Electronic address: xxb_1104@sina.cn., Yang K; Teaching hospital of Shenyang Pharmaceutical University, General Hospital of Northern Theater Command, 100016, Shenyang city, Liaoning province, PR China; Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang city, Liaoning province, PR China. Electronic address: syphuyks100@163.com., Wang S; Teaching hospital of Shenyang Pharmaceutical University, General Hospital of Northern Theater Command, 100016, Shenyang city, Liaoning province, PR China; Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang city, Liaoning province, PR China. Electronic address: ws322577@163.com., Zhang T; Teaching hospital of Shenyang Pharmaceutical University, General Hospital of Northern Theater Command, 100016, Shenyang city, Liaoning province, PR China; Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang city, Liaoning province, PR China. Electronic address: 18940967573@163.com., Hui F; Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang city, Liaoning province, PR China. Electronic address: huifuhai@163.com., Zheng F; Teaching hospital of Shenyang Pharmaceutical University, General Hospital of Northern Theater Command, 100016, Shenyang city, Liaoning province, PR China; Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang city, Liaoning province, PR China. Electronic address: zhengfangyuanzxq@163.com., Geng H; Teaching hospital of Shenyang Pharmaceutical University, General Hospital of Northern Theater Command, 100016, Shenyang city, Liaoning province, PR China; Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang city, Liaoning province, PR China. Electronic address: x876892517@163.com., Xu C; Teaching hospital of Shenyang Pharmaceutical University, General Hospital of Northern Theater Command, 100016, Shenyang city, Liaoning province, PR China; Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang city, Liaoning province, PR China. Electronic address: Charlottexu1996@163.com., Xun F; Teaching hospital of Shenyang Pharmaceutical University, General Hospital of Northern Theater Command, 100016, Shenyang city, Liaoning province, PR China; General Hospital of Northern Theater Command, China Medical University, Shenyang city, Liaoning province, PR China. Electronic address: 15690510226@163.com., Xu Z; Teaching hospital of Shenyang Pharmaceutical University, General Hospital of Northern Theater Command, 100016, Shenyang city, Liaoning province, PR China; Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang city, Liaoning province, PR China. Electronic address: Xza13842350393@163.com., Wang C; Teaching hospital of Shenyang Pharmaceutical University, General Hospital of Northern Theater Command, 100016, Shenyang city, Liaoning province, PR China; Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang city, Liaoning province, PR China. Electronic address: W1877816073@outlook.com., Hou S; Luoxin Pharmaceuticals Group Stock Co., Ltd., Linyi, PR China. Electronic address: shanbohou@luoxin.cn., Song A; Luoxin Pharmaceuticals Group Stock Co., Ltd., Linyi, PR China. Electronic address: aigangsong@luoxin.cn., Ren T; Teaching hospital of Shenyang Pharmaceutical University, General Hospital of Northern Theater Command, 100016, Shenyang city, Liaoning province, PR China; Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang city, Liaoning province, PR China. Electronic address: sz_pharm@163.com., Zhao Q; Teaching hospital of Shenyang Pharmaceutical University, General Hospital of Northern Theater Command, 100016, Shenyang city, Liaoning province, PR China; Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang city, Liaoning province, PR China. Electronic address: zhaoqingchun1967@163.com.
Jazyk:	angličtina
Zdroj:	European journal of pharmacology [Eur J Pharmacol] 2024 Nov 15; Vol. 983, pp. 176952. Date of Electronic Publication: 2024 Aug 30.
DOI:	10.1016/j.ejphar.2024.176952
Abstrakt:	Background: Inhibiting PI3K/AKT pathway activation may hinder the occurrence and progression of cancer. The aim of this study was to evaluate the efficacy and safety of the PI3K/AKT inhibitors and determine the most appropriate inhibitor for different cancer types. Methods: Electronic databases up to June 2024 were used to examine the efficacy and safety of PI3K inhibitors (alpelisib, copanlisib, duvelisib, and idelalisib) and AKT inhibitors (capivasertib, ipatasertib and MK-2206) for the treatment of cancer. Data was assessed with a random-effect pairwise and network meta-analysis. Randomized controlled trials and retrospective studies were eligible if they compared PI3K or AKT inhibitors with non-PI3K/AKT controls with no restriction. Results: The results were based on 34 studies from 34 published articles and 6 online registration trials (6710 patients). According to pairwise meta-analysis, PI3K/AKT inhibitors showed to be highly effective, especially for treating mutant cancers, but had poor safety profiles. According to our network meta-analysis, PI3K/AKT inhibitors, especially the AKT inhibitor capivasertib, are effective for treating solid cancers such as breast cancer (BC). Moreover, PI3K inhibitors, especially idelalisib, were effective for treating hematologic cancers such as chronic lymphocytic leukemia (CLL). Conclusions: The PI3K/AKT inhibitors are effective in patients with genetic mutations. For solid cancers such as BC, capivasertib was efficacy and safety. For hematological cancers represented by CLL, idelalisib was efficacy and safety. The above studies can be used when recommending appropriate targeted therapies for patients with different cancer types. Competing Interests: Declaration of competing interest The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. (Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze:	MEDLINE
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