The Mischel laboratory aims to elucidate the signaling networks underlying sensitivity and resistance to kinase inhibitor therapy in glioblastoma patients and to use this information to develop molecularly targeted combination therapies. This strategy is tightly coupled to the development of new diagnostic approaches for rapid detection of relevant molecular signatures in clinical samples to facilitate the successful clinical translation of kinase inhibitor therapy. Achievement of these goals has the potential both to greatly improve clinical care for glioblastoma patients, and to shed light on the successful application of molecularly targeted therapies to patients with a variety of types of cancer. The EGFR/PI3K/Akt/mTOR signaling pathway is a major focus of our work (Mellinghoff et al., NEJM 2005; Choe et al., Cancer Res., 2003; Wang et al., Cancer Res., 2006; Horvath et al., PNAS 2006; Cloughesy et al., PLoS Med., 2008).