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This Podcast features an interview with Eric Haura and Matthew Smith, authors of a Research Article that appears in the 13 January 2015 issue of Science Signaling, about an assay that may expand the identification of tumors that are likely to respond to therapies that inhibit epidermal growth factor receptor (EGFR) signaling. EGFR is a transmembrane receptor tyrosine kinase that induces intracellular signaling in response to binding to extracellular ligands, such as growth factors and cytokines. EGFR signaling is abnormally highly active and drives tumor cell proliferation in diverse types of cancer. Drugs that target EGFR are used to treat some of these cancers. Aberrant EGFR signaling may result from activating mutations, which can be detected by genetic analysis of the tumor cells. However, there may be other causes for increased EGFR signaling in cancer cells in addition to those that can be detected by gene sequencing. Smith et al. have developed an assay that can detect increased EGFR signaling in cancer cells by measuring the interaction of EGFR with the adaptor protein GRB2, which is required for EGFR signaling. The assay detects aberrant EGFR signaling even in tumors with no activating mutations in EGFR. This assay could be used to improve identification and treatment of EGFR-driven cancers.