The PI3K pathway in human disease
By D. Fruman, Honyin Chiu, B. Hopkins, S. Bagrodia, Lewis C. Cantley, R. Abraham. Cell, 2017
2,352 citations recorded by the source corpus.
Phosphoinositide 3-kinase (PI3K) activity is stimulated by diverse oncogenes and growth factor receptors, and elevated PI3K signaling is considered a hallmark of cancer. Many PI3K pathway-targeted therapies have been tested in oncology trials, resulting in regulatory approval of one isoform-selective inhibitor (idelalisib) for treatment of certain blood cancers, and a variety of other agents at different stages of development. In parallel to PI3K research by cancer biologists, investigations in other fields have uncovered exciting and often unpredicted roles for PI3K catalytic and regulatory subunits in normal cell function and in disease. Many of these functions impinge upon oncology by influencing the efficacy and toxicity of PI3K-targeted therapies. Here we provide a perspective on the roles of class I PI3Ks in the regulation of cellular metabolism and in immune system functions, two topics closely intertwined with cancer biology. We also discuss recent progress developing PI3K-targeted therapies for treatment of cancer and other diseases.
Subfields: Genetics, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/3b7693c9b318572480311a48a44153259b9f1cbb
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In Molecular Biology
- B. Hopkins
- Lewis C. Cantley
- Guolong Zhang
- Jeremy M. Baskin
- David M. Sabatini
- M. V. Vander Heiden
- J. Engelman
- P. Pandolfi
Citations in the corpus
- JMJD8 Promotes Malignant Progression of Lung Cancer by Maintaining EGFR Stability and EGFR/PI3K/AKT Pathway Activation (2021, background): “PI3Ks can be divided into three categories; the IA class is the most extensive, and includes the p85 regulatory subunit and the p110 catalytic subunit [10, 11].”
- Branched Chain Amino Acids: Beyond Nutrition Metabolism (2018, background): “The PI3K, as a nuclear factor, participate in many biological processes, and plays a critical role in cellular functions including immunity, growth, and survival in cellular signaling pathways [8,33,34].”
- PIP4Ks Suppress Insulin Signaling through a Catalytic-Independent Mechanism (2018, positive): “PI(4,5) P 2 is also the substrate that class 1 phosphoinositide 3-kinases use (Saito et al., 2003) to generate the second messenger phosphatidylinositol-3,4,5-trisphosphate (PI(3,4,5)P 3 ) in response to insulin and other growth factors (Fruman et al., 2017).”
- Targeting PI3K/Akt signal transduction for cancer therapy (2021, background): “TEC family proteins, such as BTK, play a key role in PI3K signal transduction.(183) BTK inhibition reduces the output of the PI3K signal in B cells.”