Erlotinib enhances the proapoptotic activity of cytotoxic agents and synergizes with paclitaxel in poorly-differentiated thyroid carcinoma cells.

Background: The therapeutic role of EGFR inhibitors in thyroid malignancies is still controversial even though the full activation of EGF signaling has recently been proposed as involved in the dedifferentiation of human thyroid cancers. Materials and Methods: Agents which target EGFR signaling (erlotinib, cetuximab and panitumumab) were evaluated at preclinical level in a panel of thyroid tumor cell lines. Results: Erlotinib induced a dose-dependent inhibition of cell proliferation together with inhibition of EGF-induced AKT and ERK1/2 signaling only in poorly-differentiated thyroid carcinoma FRO cells. By contrast, anti-EGFR monoclonal antibodies were inactive. Of note, erlotinib enhanced the proapoptotic activity of doxorubicin and paclitaxel and exhibited synergy with paclitaxel in poorly-differentiated thyroid carcinoma cells. Conclusion: EGFR signaling may represent a molecular target only in poorly-differentiated thyroid carcinoma cells, and agents that inhibit EGFR tyrosine kinase may be more effective than monoclonal antibodies which target the extracellular domain of the receptor.