Abstract 725: eIF4E/4eBP-1 as predictive factor(s) of response to EGFR targeted drug in head and neck cancer

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL Purpose: There is a clinical need to identify predictive markers of the response to epidermal growth factor receptor (EGFR) inhibitors in patients with head and neck squamous cell carcinoma (HNSCC). In breast cancer, the resistance to targeted therapies against HER2 implicates the reactivation of the PI3K/Akt/mTOR pathway and eIF4E overexpression. The axis eIF4E/4eBP-1 is one of the major downstream effector of the PI3K/Akt/mTOR pathway. The aim of this study was to further investigate these markers in the response to preclinical and clinical EGFR inhibitors used in HNSCC, cell lines and patients. Experimental Design: We studied the effects of cetuximab using human HNSCC cell lines (CAL33 and CAL166) on proliferation, survival pathways, eIF4E and 4eBP activities and expression by western blot or immunohistochemistry in initial biopsies of patients treated for an HNSCC with cetuximab used in combination with radiotherapy or cisplatin (n=28). Results: The HNSCC cell lines have an opposite effect under cetuximab treatment. Whereas the CAL33 are not sensitive, the CAL166 shows a moderate cytostatic effect allowing us to determine an IC20 of 5,56 +/− 0.37 µg/mL. In the CAL33 cell lines cetuximab doesn't significantly modify the 4eBP phosphorylation level. On the contrary in CAL166 cetuximab induces the inhibition of the 4eBP phosphorylation level corroborating the cytostatic effect previously observed. More over, in patients the combination Cetuximab / radiotherapy or cisplatin shows, in the initial biopsie examination in the non-responder group, a significant higher level of eIF4E. Conclusion: The couple eIF4E expression levels and/or activities appeared to be determinant to discriminate the response to the EGFR targeted inhibitor in HNSCC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 725. doi:1538-7445.AM2012-725