Journal article
K-Ras mutation and amplification status is predictive of resistance and high basal pAKT is predictive of sensitivity to everolimus in biliary tract cancer cell lines
Y Yeung, DK Lau, F Chionh, H Tran, JWT Tse, AJ Weickhardt, M Nikfarjam, AM Scott, NC Tebbutt, JM Mariadason
Molecular Oncology | WILEY | Published : 2017
Abstract
Advanced biliary tract cancer (BTC) has a poor prognosis and limited treatment options. The PI3K/Akt/mTOR signalling pathway is hyperactivated in a subset of BTCs, and clinical activity of the mTOR inhibitor everolimus has been observed in some patients with BTC. The goal of this study was to identify biomarkers predictive of everolimus response. Twenty BTC cell lines were assessed for everolimus sensitivity with a spectrum of growth inhibitory responses observed. Molecular biomarkers of sensitivity and resistance were identified by interrogation of the activation status of the Ras/MAPK and PI3K/Akt/mTOR pathways. K-Ras mutations and/or amplifications were identified in 45% of cell lines and..
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Awarded by Victorian Cancer Agency
Funding Acknowledgements
This project was supported by the Victorian Cancer Agency (TRP13083), a NHMRC Senior Research Fellowship (1046092) to JMM, a NHMRC Senior Practitioner Fellowship (1084178) to AMS, a NHMRC Postgraduate Research Scholarship (1017737) to FC, Ludwig Cancer Research and the Operational Infrastructure Support Program, Victorian Government, Australia. YY was supported by a Fellowship from the ANZ Trustees Foundation - Brian Smith Endowment. DL and JT were supported by Australian Postgraduate Awards and DL by a scholarship from the Pancare Foundation.