PI3K pathway alterations in cancer: variations on a theme

By T. Yuan, Lewis C. Cantley. Oncogene, 2008

1,916 citations recorded by the source corpus.

The high frequency of phosphoinositide 3-kinase (PI3K) pathway alterations in cancer has led to a surge in the development of PI3K inhibitors. Many of these targeted therapies are currently in clinical trials and show great promise for the treatment of PI3K-addicted tumors. These recent developments call for a re-evaluation of the oncogenic mechanisms behind PI3K pathway alterations. This pathway is unique in that every major node is frequently mutated or amplified in a wide variety of solid tumors. Receptor tyrosine kinases upstream of PI3K, the p110α catalytic subunit of PI3K, the downstream kinase, AKT, and the negative regulator, PTEN, are all frequently altered in cancer. In this review, we will examine the oncogenic properties of these genetic alterations to understand whether they are redundant or distinct and propose treatment strategies tailored for these genetic lesions.

Subfields: Genetics, Molecular Biology, Pulmonary and Respiratory Medicine

View Paper: https://www.semanticscholar.org/paper/d02d36830d9140811a5b814d4dd28754ac2d45a1

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Citations in the corpus

Hallmarks of cancer: the next generation. (2011, positive): “Similarly, mutations in the catalytic subunit of phosphoinositide 3-kinase (PI3-kinase) isoforms are being detected in an array of tumor types, which serve to hyperactivate the PI3kinase signaling circuitry, including its key Akt/PKB signal transducer (Jiang and Liu, 2009; Yuan and Cantley, 2008).”
ErbB receptors and signaling pathways in cancer. (2009, background): “The PI3K/Akt pathway is dysregulated in most human tumors by mutations affecting various proteins on the pathway [34].”
The RAS/RAF/MEK/ERK and the PI3K/AKT signalling pathways: role in cancer pathogenesis and implications for therapeutic approaches (2012, background): “PI3Ks belong to a conserved family of lipid kinases that phosphorylate the 3¢-hydroxyl group of phosphoinositides [11].”
Principles and Current Strategies for Targeting Autophagy for Cancer Treatment (2011, background): “Thus, the vast majority of cancers have some degree of aberrant activation of the PI3K-AktmTOR signaling axis (50).”
A novel pathway combining calreticulin exposure and ATP secretion in immunogenic cancer cell death (2012, positive): “Since, wortmannin tends to exhibit a high afﬁnity for the p110 a domain of the PI3K protein (Campos-Toimil et al , 2002; Yuan and Cantley, 2008) we used a small hairpin RNA (shRNA) to stably deplete the PI3K p110 a protein in CT26 cancer cells (Supplementary Figure S9C) in order to conﬁrm the…”
Monoacylglycerol lipase regulates a fatty acid network that promotes cancer pathogenesis (2010, background): “…which is formed by the action of phosphatidylinositol-3-kinase and activates protein kinase B/Akt to promote cell proliferation and survival (Yuan and Cantley, 2008; Zunder et al., 2008); (2) lysophosphatidic acid (LPA), which signals through a family of G protein-coupled receptors to…”
Post operative radiation therapy in endometrial carcinoma : reducing overtreatment and improving quality of life (2013, background): “These independent alterations activate the PI3K-AKT pathway differently, and cumulative molecular alterations may have a selective advantage.(29) It may be possible that loss of PTEN results in circumvention of negative feedback loops which result in an additive effect on PI3K-AKT pathway activation”
Immunogenic cell death and DAMPs in cancer therapy (2012, background): “These authors showed that a recombinant N-terminal fragment of CRT (39-272) is a potent inducer of activation and maturation of B cells and macrophages and can trigger Ig class switching in B cells without T cell help in vitro and in vivo72.”
STAT3 activation of miR-21 and miR-181b-1, via PTEN and CYLD, are part of the epigenetic switch linking inflammation to cancer (2010, background): “PTEN is an upstream regulator of Akt kinase pathway that is involved in oncogenesis (Yuan and Cantley, 2008).”