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Non-Small Cell Lung Cancer Genetic Predictors

Non-Small Cell Lung Cancer Genetic Predictors. Sacha Rothschild, MD PhD Medical Oncology. The genomic evolution of lung adenocarcinoma. Pao et al. Lancet Oncol 2011; Pao and Hutchinson. Nat Med 2012.

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Non-Small Cell Lung Cancer Genetic Predictors

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  1. Non-Small Cell Lung CancerGenetic Predictors Sacha Rothschild, MD PhD Medical Oncology

  2. The genomicevolutionoflungadenocarcinoma Pao et al. Lancet Oncol 2011; Pao and Hutchinson. Nat Med 2012 NSCLC Symposium St. Gallen - Genetic Predictors

  3. Survival of patients with oncogenic drivers – targeted therapy vs. no targeted therapy Kris et al. Abstract PL03-07 NSCLC Symposium St. Gallen - Genetic Predictors

  4. Mutations in the EGFR tyrosine kinase domain Pao W, et al. PNAS 2004; Paez J, et al. Science 2004 NSCLC Symposium St. Gallen - Genetic Predictors

  5. EGFR-TKIs vs. Chemotherapy as first-line therapy 7 randomizedtrialsconfirmingtheroleoffirst-line EGFR-TKI in patientswith EGFR-mutatedadenocarcinoma 1Mok et al. NEJM 2009; 2Lee et al. WCLC 2009; 3Mitsudomi et al. Lancet Oncol 2010; 4Maemondo et al. NEJM 2010; 5Zhou et al. ESMO 2010; 6Rosell et al. Lancet Oncol 2012; 7Yang et al. ASCO 2012; abstract LBA7500 NSCLC Symposium St. Gallen - Genetic Predictors

  6. Mechanismsof Resistance to EGFR kinaseinhibitors in EGFR mutant NSCLC Yu HA, et al. Clin Cancer Res 2013;19:2240-7 NSCLC Symposium St. Gallen - Genetic Predictors

  7. EML4-ALK translocations in NSCLC • EML4-ALK frequency: ~ 4% • Primarily in adenocarcinoma • More common in younger patients • More common in never-smokers Soda M et al. Nature 2007; 448:561-566.Koivunen et al. CCR 2008 NSCLC Symposium St. Gallen - Genetic Predictors

  8. PROFILE 1007 – PFS by independent radiologic review Median PFS: 7.7 vs. 3.0 months Shaw AT, et al. NEJM 2013;368:2385-94 NSCLC Symposium St. Gallen - Genetic Predictors

  9. ALK-inhibitor resistance mechanisms in ALK-positive NSCLC Doebele RC, et al. ClinCancer Res 2012;18:1472-82; Shaw AT, et al. ASCO 2013; abstract 8010 NSCLC Symposium St. Gallen - Genetic Predictors

  10. ROS1 • Receptortyrosinekinaseoftheinsulinreceptorfamily • 1-2% oflungadenocarcinomaspecimensharbor ROS1 fusionabnormality • More common in never-smokersand Asian patients • ROS1 fusionwiththetransmembranesolutecarrierprotein SLC34A2 results in a constitutivekinaseactivity in a NSCLC cellline Rikova, et al. Cell 2007; Takeuchi, et a. Nat Med 2011; Bergethon, et al. JCO 2012; Oxnard et al. J ClinOncol 2013 NSCLC Symposium St. Gallen - Genetic Predictors

  11. Crizotinib in ROS1 positive NSCLC – a phase II study Ou et al. Abstract O16.07 NSCLC Symposium St. Gallen - Genetic Predictors

  12. RAS signallingnetworks Kamauband Weinberg, Nat Rev 2008 NSCLC Symposium St. Gallen - Genetic Predictors

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