Targeting the phosphoinositide 3-kinase (PI3K) pathway in cancer

By Pixu Liu, Hailing Cheng, T. Roberts, Jean J. Zhao. Nature reviews. Drug discovery, 2009

2,573 citations recorded by the source corpus.

The phosphoinositide 3-kinase (PI3K) pathway is a key signal transduction system that links oncogenes and multiple receptor classes to many essential cellular functions, and is perhaps the most commonly activated signalling pathway in human cancer. This pathway therefore presents both an opportunity and a challenge for cancer therapy. Even as inhibitors that target PI3K isoforms and other major nodes in the pathway, including AKT and mammalian target of rapamycin (mTOR), reach clinical trials, major issues remain. Here, we highlight recent progress that has been made in our understanding of the PI3K pathway and discuss the potential of and challenges for the development of therapeutic agents that target this pathway in cancer.

Subfields: Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/0a9ea96b737d5dad2480be9ac88c9c5e0dbd2cf1

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Citations in the corpus

The nuts and bolts of AGC protein kinases (2010, background): “Several compounds targeting these signal transduction pathways are in clinical trials, including inhibitors of PI3K (GDC0941; Genentech), mTOR (AZD8055; Astra Zeneca), mTORC1 (rapamycin (also known as sirolimus; Rappamune; Wyeth)), temsirolimus (Torisel; Wyeth), everolimus (Afinitor or Certican; Nov”
PI3K/AKT/mTOR signaling transduction pathway and targeted therapies in cancer (2023, background): “Potentially, pan-PI3Ki provide a broader range of activity by comprising numerous molecular targets, although exists increasing risk of on-target and off-target toxicity [209].”
The secret ally: immunostimulation by anticancer drugs (2012, background): “Owing to the crucial role of phosphoinositide 3-kinases (PI3Ks) in multiple aspects of cell biology, the PI3K network constitutes an attractive target for anticancer therap”
Reciprocal feedback regulation of PI3K and androgen receptor signaling in PTEN-deficient prostate cancer. (2011, background): “The PI3K pathway plays a central role in tumorigenesis across a variety of malignancies (Courtney et al., 2010; Liu et al., 2009).”
Glioma Subclassifications and Their Clinical Significance (2017, background): “EGFR is a receptor tyrosine kinase that activates P13/AKT mitogenic pathways, resulting in activation of MTOR, an enzyme that is key to increase angiogenesis, proliferation, and survival of tumor cells [87].”
The RAS/RAF/MEK/ERK and the PI3K/AKT signalling pathways: role in cancer pathogenesis and implications for therapeutic approaches (2012, background): “1% 3% [4] [4] [12] AKT3 Mutation Melanoma 1.”
Erk2 phosphorylation of Drp1 promotes mitochondrial fission and MAPK-driven tumor growth (2015, background): “, 2003) pathways have been developed and shown to have antitumor activity, and there are numerous clinical trials testing such inhibitors for the treatment of a broad spectrum of cancers (Liu et al., 2009; Montagut and Settleman, 2009).”
PARP Inhibitors: Clinical Relevance, Mechanisms of Action and Tumor Resistance (2020, background): “The use of PI3k inhibitors in cancer therapy has been well established, given the PI3k pathway has been suggested to be one of the most commonly activated pathways in cancer cells (Liu et al., 2009).”
Targeting the PI3K pathway in cancer: are we making headway? (2018, background): “Convergent loss of PTEN leads to clinical resistance to a PI(3)Kα inhibitor.”
Breast cancer development and progression: Risk factors, cancer stem cells, signaling pathways, genomics, and molecular pathogenesis (2018, background): “Interestingly, PIK3CA gene amplification was reported even before PIK3CA mutations were identified, and was found in various malignancies, including approximately 10% of cases of breast cancer.(235,236) In addition to PIK3CA mutations, there are many other PI3K-enhancing mechanisms, such as HER2 amp”
Autophagy as a target for anticancer therapy (2011, background): “From the molecular standpoint, the processes elucidated above are often controlled by the PI3K/Akt/mTOR pathway, which is frequently activated in cancer cells, and which drives growth and proliferation as well as nutrient availability”
Signaling mechanisms of the epithelial-mesenchymal transition (2014, background): “Additionally, PDGF induces the phosphorylation of the nuclear RNA helicase p68, which promotes EMT through the nuclear translocation of β-catenin in a Wnt-independent manner in various epithelial cancer cell lines (114).”