Exploiting the PI3K/AKT Pathway for Cancer Drug Discovery

By Bryan T. J. Hennessy, Debra L. Smith, Prahlad T. Ram, Yiling Lu, Gordon B. Mills. Nature reviews. Drug discovery, 2005

2,176 citations recorded by the source corpus.

Subfields: Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/d80612dc7c223952c0cf87b586a67cc6a72f6f65

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Genetics

In Molecular Biology

Citations in the corpus

Targeting PI3K/Akt/mTOR Signaling in Cancer (2014, background): “Thus, this complex pathway has been taken into consideration as one of the most attractive targets for the development of anticancer agents (3, 4).”
Targeting the phosphoinositide 3-kinase (PI3K) pathway in cancer (2009, background): “These findings, and the fact that PI3K and other kinases in the PI3K pathway are amenable to pharmacological intervention, make this pathway one of the most attractive targets for therapeutic intervention in cance”
Integrating virtual screening and combinatorial chemistry for accelerated drug discovery. (2011, background): “AKT is frequently amplified and overexpressed in human cancer cells and its inhibition is a promising therapeutic approach for the treatment of cancers [65].”
Targeting PI3K/Akt signal transduction for cancer therapy (2021, background): “The PI3K/Akt pathway can be aberrantly activated through various mechanisms, including different genomic alterations, such as mutations of PIK3CA, phosphatase and tensin homolog (PTEN), Akt, TSC1, and mechanistic target of rapamycin (mTOR).(2) PI3K phosphorylates phosphatidylinositol-4,5-bisphosphat”
mTOR, translation initiation and cancer (2006, background): “An important downstream target of this signaling pathway is cap-dependent mRNA translation (Hay and Sonenberg, 2004; Hennessy et al., 2005; Stephens et al., 2005; Petroulakis et al., 2006) (Figure 2). mTOR promotes the phosphorylation and activation of S6K and the hierarchial phosphorylation the…”
Ligand-independent HER2/HER3/PI3K complex is disrupted by trastuzumab and is effectively inhibited by the PI3K inhibitor GDC-0941. (2009, background): “Several properties that are critical for therapeutic agents differentiate GDC-0941 from previously tested PI3K inhibitors, including wortmannin and LY294002 (Bain et al., 2007; Hennessy et al., 2005; Nagata et al., 2004).”
Targeting phosphoinositide 3-kinase: moving towards therapy. (2008, background): “Additionally, mutations have been identified in activators of PI3K, like the epidermal growth factor receptor (EGFR), the platelet-derived growth factor receptor (PDGFR) and Bcr-Abl [5,132,134].”
p53 and metabolism (2009, background): “These include not only AKT, which is frequently activated in human cancers through various mechanism”
Hyperactive Ras in developmental disorders and cancer (2007, background): “Akt is a kinase that promotes survival in many cell types by phosphorylating and therefore inactivating several pro-apoptotic proteins including BAD and Forkhead ( FKHR ) transcription factor”
PI3K/AKT/mTOR signaling transduction pathway and targeted therapies in cancer (2023, background): “In addition, PAM pathway hyperactivation in cancer frequently underpins the development of treatment resistance [11, 14, 18].”
A dual PI3 kinase/mTOR inhibitor reveals emergent efficacy in glioma. (2006, positive): “…kinase family highlight the fact that genetic disruption of the pathway can induce compensatory or unanticipated alterations in the activities of key regulatory proteins; for this reason, kinase-dead and kinase-absent mutations often induce different phenotypes (reviewed in Hennessy et al., 2005).”
Signal transduction by focal adhesion kinase in cancer (2009, background): “Phospholipid production stimulated by FAK association and activation of PI3K can activate Akt kinase, which inhibits apoptosis by regulating various cell death machinery proteins [31, 32].”
Phosphoinositides: tiny lipids with giant impact on cell regulation. (2013, background): “The close connection between PI3K activation and mTORC1 (and -2) (1830) and the characteristic metabolic realignment of cancer cells (930, 1608, 1769) explain why PI3K inhibitors and mTOR inhibitors are both in the frontiers as potential cancer therapies and that combined PI3K/mTOR inhibitors are al”