| Project Overview: | We have initiated a project to look for determinants of sensitivity and resistance to erlotinib in lung cancer. This drug is especially effective in lung cancer patients that have activating mutations in the EGF receptor. Although the tumours initially regress, the tumours eventually become resistant to the drug. It has been described that in some cases tumours develop a second mutation in the EGF receptor, or start to express high levels of another growth factor receptor. However, the mechanism of resistance in about 40-50% of the tumours is unknown. To identify novel mechanisms by which tumour cells can acquire resistance to erlotinib, I plan to perform an siRNA screen by which we can down-regulate the expression of a large number of proteins individually. The proteins of interest will be the ones whose knock down results in resistance of normally erlotinib-sensitive cells to erlotinib treatment, as these will shed light on the signal transduction pathways that are involved in drug resistance. We hope identifying these proteins will provide pointers for novel therapeutic directions in erlotinib resistant disease. Ultimately we plan to check the expression of proteins implicated by our screen in erlotinib resistance in human tumour samples of known erlotinib resistance status and also in tumours from a mouse EGFR driven lung cancer model where erlotinib resistance may develop following prolonged treatment. |
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| Screener: | Elza De Bruin (Downward Lab). Extension:3365, Rm 206 |
| Project Status: | Published |
| Publications: | Reduced NF1 expression confers resistance to EGFR inhibition in lung cancer.. de Bruin et al., 2014 |
| Project Start Date: | Oct 2009 |
| Keywords: | Erlotinib Lung Cancer Viability |
| Libraries Screened: |
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