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MINI 14 - Pre-Clinical Therapy (ID 119)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:L. Fernandez-Cuesta, A.F. Gazdar
- Coordinates: 9/08/2015, 10:45 - 12:15, Mile High Ballroom 2c-3c
MINI14.13 - Small Molecule Demonstrates Potent Tumor Suppression by Inhibiting the PI3K/AKT Pathway in Non-Small Cell Lung Cancer (ID 721)
10:45 - 12:15 | Author(s): J. Crockard
The phosphoinositide 3-kinase (PI3K) / protein kinase B (AKT) / mammalian target of rapamycin (mTOR) pathway is frequently activated in many malignancies including non-small cell lung cancer (NSCLC). Dysregulation of this pathway leads drives oncogenic genes and imparts resistance to conventional chemotherapy. We identified a small molecule AKT pathway inhibitor as a potential lead compound.
The AKT pathway inhibitor was tested in vitro on a panel of NSCLC cell lines A427, A549, NCI-H1703, NCI-H2170, NCI-H1650, and NCI-H1975. Cell viability was determined by MTS assay after 72 hours of drug treatment. Activation kinases in the PI3K/AKT/mTOR pathway was determined by western blot analysis.
Treatment with the PI3K/AKT pathway inhibitor caused potent concentration-dependent inhibition of cell proliferation with a half maximal inhibitory concentration (IC~50~) in the nanomolar range. Kirsten rat sarcoma (KRAS) mutant cell lines were the most sensitivity to the PI3K/AKT pathway inhibitor while epidermal growth factor receptor (EGFR) mutant cell lines were more resistant. Western blot analysis showed inhibition of AKT and mTOR phosphorylation at nanomolar concentrations.
A novel small molecule AKT inhibitor inhibits growth of NSCLC cells in vitro, is potent against KRAS mutants, and shows promise as a small molecule targeted chemotherapy drug for NSCLC.
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