Targeting PI3K/Akt signal transduction for cancer therapy
By Yan He, Miao-miao Sun, Guo Geng Zhang, Jing Yang, Kui-Sheng Chen, W. Xu, Bin Li. Signal Transduction and Targeted Therapy, 2021
1,686 citations recorded by the source corpus.
The phosphatidylinositol 3-kinase (PI3K)/Akt pathway plays a crucial role in various cellular processes and is aberrantly activated in cancers, contributing to the occurrence and progression of tumors. Examining the upstream and downstream nodes of this pathway could allow full elucidation of its function. Based on accumulating evidence, strategies targeting major components of the pathway might provide new insights for cancer drug discovery. Researchers have explored the use of some inhibitors targeting this pathway to block survival pathways. However, because oncogenic PI3K pathway activation occurs through various mechanisms, the clinical efficacies of these inhibitors are limited. Moreover, pathway activation is accompanied by the development of therapeutic resistance. Therefore, strategies involving pathway inhibitors and other cancer treatments in combination might solve the therapeutic dilemma. In this review, we discuss the roles of the PI3K/Akt pathway in various cancer phenotypes, review the current statuses of different PI3K/Akt inhibitors, and introduce combination therapies consisting of signaling inhibitors and conventional cancer therapies. The information presented herein suggests that cascading inhibitors of the PI3K/Akt signaling pathway, either alone or in combination with other therapies, are the most effective treatment strategy for cancer.
Subfields: Molecular Biology, Oncology, Pathology and Forensic Medicine
View Paper: https://www.semanticscholar.org/paper/8ee8930e0c51b7bb9bbef472942e2242fe1debb5
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Citations in the corpus
- PI3K/AKT/mTOR signaling transduction pathway and targeted therapies in cancer (2023, background): “Alterations in epidermal growth factor receptor (EGFR) [36, 37], fibroblast growth factor receptor (FGFR) [38, 39], platelet-derived growth factor receptor (PDGFR) [40, 41], vascular endothelial growth factor receptor (VEGFR) [42, 43], hepatocyte growth factor (HGF) [44, 45], leukocyte receptor tyro”
- NF-κB in biology and targeted therapy: new insights and translational implications (2024, background): “85 IKK α binds to p100 and phosphorylates serines 99, 108, 115, 123, and 872 on p100.”
- Multifaceted role of mTOR (mammalian target of rapamycin) signaling pathway in human health and disease (2023, background): “The dual PI3K/mTOR inhibition has emerged as a critical strategy to target mTOR signaling in human malignancies.(321) For instance, NVP-BEZ235 (dactolisib) was shown to suppress the PI3K isoforms, mTOR, and ATR which resulted in strong anticancer activity in both solid and blood cancers.”
- Current landscape and future directions of therapeutic approaches for adenoid cystic carcinoma of the salivary glands (Review) (2025, unknown): “PI3K activates AKT by phosphorylation and via certain transcriptional factors, including mTOR (107).”