Utilizing combinations of molecular targeted agents to sensitize tumor cells to EGFR inhibitors

EGFR inhibitors have achieved clinical antitumor activity as single agents. The specific inhibition of EGFR and associated pathways provides a mechanism for efficacious inhibition of tumor cell growth while minimizing toxicities often associated with chemotherapeutic drugs. The challenge of using targeted cancer drugs as single agents is the potential for de novo or acquired resistance due to established or adapted alternate signal transduction pathways. In this chapter, we will describe how cancer drug combinations with EGFR inhibitors can be rationally identified by utilizing our understanding of the molecular mechanism and related biomarkers of EGFR inhibitor sensitivity. Such combinations may ultimately provide better efficacy and reduced toxicity for patients.