Akt/protein kinase B is constitutively active in non-small cell lung cancer cells and promotes cellular survival and resistance to chemotherapy and radiation.

By J. Brognard, A. Clark, Yucheng Ni, P. Dennis. Cancer Research, 2001

947 citations recorded by the source corpus.

View Paper: https://www.semanticscholar.org/paper/eddd4c9678bc77230515971a7b9eefda4d18815f

How researchers see this paper

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

1. K. West
2. J. Brognard
3. Tianyan Gao
4. E. Sierecki
5. A. Newton
6. S. Castillo
7. P. Dennis
8. A. Clark

Citations in the corpus

• PHLPP: a phosphatase that directly dephosphorylates Akt, promotes apoptosis, and suppresses tumor growth. (2005, background): “H157 cells are derived from nonmall cell lung cancers and have elevated Akt phoshorylation and low apoptosis (Brognard et al., 2001).”
• Activation of the PI3K/Akt pathway and chemotherapeutic resistance. (2002, background): “In studies with non-small cell lung cancer cells performed in our laboratory, LY294002 treatment inhibited Akt phosphorylation and activity and induced apoptosis in cells with constitutively active Akt (Brognard et al., 2001).”
• Targeting PI3K/Akt signal transduction for cancer therapy (2021, background): “Similarly, a study showed that targeting PI3K/Akt signaling pathway components can be used to overcome drug resistance in cancer therapy.(137)”
• Anti-tumor activity of GW572016: a dual tyrosine kinase inhibitor blocks EGF activation of EGFR/erbB2 and downstream Erk1/2 and AKT pathways (2002, background): “Constitutive activation of AKT has been implicated in tumor resistance to chemotherapeutic agents (Thakkar et al., 2001; Tenzer et al., 2001; Brognard et al., 2001).”
• MK-2206, an Allosteric Akt Inhibitor, Enhances Antitumor Efficacy by Standard Chemotherapeutic Agents or Molecular Targeted Drugs In vitro and In vivo (2010, background): “Dominant-negative mutants of Akt enhance the cytotoxicity of chemotherapeutic agents, suggesting an important role of Akt in drug resistance (16, 18).”
• The emerging treatment landscape of targeted therapy in non-small-cell lung cancer (2019, background): “A PI3K inhibitor (LY294002) has been reported to enhance the sensitivity of NSCLC to chemotherapy and radiation.(13) In addition, another mTOR inhibitor, temsirolimus (CCI-779), which targets molecules downstream of the PI3K pathways, has shown promising antitumor activity in phase I trials of NSCLC”
• Constitutive and inducible Akt activity promotes resistance to chemotherapy, trastuzumab, or tamoxifen in breast cancer cells. (2002, methodology): “Preparation of cell extracts, protein assays, and immunoblotting were performed as described previously (32).”
• PHLPP and a second isoform, PHLPP2, differentially attenuate the amplitude of Akt signaling by regulating distinct Akt isoforms. (2007, methodology): “In Vitro Kinase Assay Akt was immunoprecipitated from cell lysates using Akt agarose, and kinase reactions were performed using an Akt kinase assay kit (Cell Signaling) as described previously (Brognard et al., 2001).”
• SIN1/MIP1 maintains rictor-mTOR complex integrity and regulates Akt phosphorylation and substrate specificity. (2006, background): “etoposide, which are known to induce cell death in an AktFoxO pathway-dependent manner (Brognard et al., 2001; Brunet et al., 1999, 2004).”