| Approximately 25,000 cases of lung cancer each year are not linked to smoking, the majority occurring in women. These tumors are frequently dependent upon a mutation in the epidermal growth factor receptor (EGFR) gene. As a testament to the dependence on EGFR, Tarceva is a drug that inhibits EGFR and has demonstrated unprecedented responses when utilized in this population, although response is short-lived. Patients frequently develop resistance to Tarceva and these events have plagued the clinical community. Other molecular strategies to prevent such resistance are needed to progress toward establishing an effective cure for EGFR-dependent lung cancers. Combination therapy directed at multiple targets is a strategy to maximize response and minimize resistance and has been widely used in traditional cancer therapy. Likewise, targeting multiple molecules in EGFR-dependent lung cancer may prevent common mechanisms of tumor resistance. Our preliminary data show that EGFR-dependent lung tumors use a particular strategy for induction of tumor growth and survival. Furthermore, lung cancer cell lines which exhibit resistance to Tarceva due to presence of a specific mutation EGFR, or perhaps mutation of another gene, retain sensitivity to inhibitors of signaling pathway downstream EGFR. Therefore, we plan to explore the hypothesis that using two different targeted inhibitors in EGFR-dependent NSCLC may offer significant advantages in prohibiting the formation of resistance to treatment.
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