Barcelona, June 2013. Expert clinicians from the Dr Rosell Oncology Institute are co-authors of results presented at the 2013 annual meeting of the American Society of Clinical Oncology (ASCO). Results presented include analyses of predictive biomarkers and novel mechanisms of resistance to targeted therapies, as well as the early results of whole exome and transcriptome sequencing in collaboration with the US Cancer Therapeutics Innovation Group (GTIC). Results of the studies were presented during the congress in the form of oral presentations and posters.Integrated genomic analysis of EGFR-mutant non-small cell lung cancer immediately following erlotinib initiation in patients Trever Grant Bivona et al.Major obstacles limiting the clinical success of EGFR TKI therapy in non-small cell lung cancer (NSCLC) patients are heterogeneity and variability in the initial anti-tumor response to treatment. The underlying molecular basis for this heterogeneity has not been explored in patients immediately after initiation of therapy. We conducted CT-guided core needle biopsies immediately prior to erlotinib treatment initiation and at 6 days post erlotinib initiation in a patient with histologically confirmed NSCLC harboring an established activating mutation in EGFR. DNA from the paired frozen biopsies and matched normal tissue was analyzed by whole exome sequencing and RNA from the biopsies was analyzed by whole transcriptome sequencing. We documented the feasibility, safety and utility of this strategy to establish initial drug efficacy at the molecular level prior to any radiographic evidence of response. Abstract #117381 PosterFibroblast growth factor receptor 1 (FGFR1) and SRY-related HMG-box (SOX2) amplification in squamous cell carcinoma (SCC) of the lungAmaya Gascó et al.SOX2 is a key transcription factor that is amplified in lung SCC. FGFR1 is a receptor tyrosine kinase that promotes cell proliferation, survival and apoptotic resistance through the PLCγ/PKC, RAS/MAPK and PI3K-AKT pathways, respectively. FGFR1 is amplified in 15-25% of lung SCC. FGFR1 and SOX2 co-amplification could represent a novel therapeutic target and warrants further research. Abstract #112859 Poster DiscussionNon-disruptive mutations of TP53 and overall survival in advanced non-small-cell lung cancer (NSCLC) patientsEnric Carcereny et al.The tumor suppressor TP53 is the most commonly mutated gene in lung cancer. Early-stage NSCLC patients with TP53 mutations may have worse prognosis and be more radio/chemoresistant. However, few studies have addressed the issue of TP53 mutations in advanced NSCLC. We have retrospectively examined the influence of TP53 mutations on overall survival in 241 advanced NSCLC patients. Non-disruptive mutations in the TP53 gene are associated with shorter overall survival in advanced NSCLC patients, both in EGFR-wt patients treated with chemotherapy and in EGFR-mutant patients treated with erlotinib. These patients could benefit from treatment to reactivate mutant p53. Abstract #111773 Poster DiscussionROR1 mRNA expression in EGFR-mutant non-small-cell lung cancer (NSCLC) patients with the T790M mutation: a potential therapeutic target Niki Karachaliou et al.Progression-free survival is short in NSCLC driven by EGFR mutations treated with erlotinib alone, due to crosstalk with other signaling pathways that can cause secondary dependency. ROR1 knockdown inhibited the growth of NCI-H1975 cells (with EGFR L858R and T790M mutations). A pro-survival function for ROR1/MEK/ERK signaling has been demonstrated, with cooperation with AKT. In a subset of 95 p in the EURTAC trial (clinicaltrials.gov NCT00446225), 65% had pre-treatment T790M mutations. We have assessed ROR1 expression in 45 of these 95 patients. High ROR1 expression significantly limits progression-free survival in patients with T790M mutations. ROR1-directed therapies can enhance the efficacy of erlotinib in EGFR-mutant NSCLC patients overexpressing ROR1. Abstract #110231 Poster Discussion