High NOTCH activity induces radiation resistance in non small cell lung cancer
- Theys, J.
- Yahyanejad, S.
- Habets, R.
- Span, P.N.
- Dubois, L.
- Paesmans, K.
- Kattenbeld, B.
- Cleutjens, J.
- Groot, A.J.
- Schuurbiers, O.C.J.
- Lambin, P.
- Bussink, J.
- Vooijs, M.
DOIAbstract
BACKGROUND AND PURPOSE: Patients with advanced NSCLC have survival rates <15%. The NOTCH pathway plays an important role during lung development and physiology but is often deregulated in lung cancer, making it a potential therapeutic target. We investigated NOTCH signaling in NSCLC and hypothesized that high NOTCH activity contributes to radiation resistance. MATERIALS AND METHODS: NOTCH signaling in NSCLC patient samples was investigated using quantitative RT-PCR. H460 NSCLC cells with either high or blocked NOTCH activity were generated and their radiation sensitivity monitored using clonogenic assays. In vivo, xenograft tumors were irradiated and response assessed using growth delay. Microenvironmental parameters were analyzed by immuno...
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