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Daniel Morgensztern, MD, Meghan J. Campo, MD, Suzanne E

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Presentation on theme: "Daniel Morgensztern, MD, Meghan J. Campo, MD, Suzanne E"— Presentation transcript:

1 Molecularly Targeted Therapies in Non–Small-Cell Lung Cancer Annual Update 2014 
Daniel Morgensztern, MD, Meghan J. Campo, MD, Suzanne E. Dahlberg, PhD, Robert C. Doebele, MD, PhD, Edward Garon, MD, David E. Gerber, MD, Sarah B. Goldberg, MD, Peter S. Hammerman, MD, PhD, Rebecca S. Heist, MD, Thomas Hensing, MD, Leora Horn, MD, Suresh S. Ramalingam, MD, Charles M. Rudin, MD, PhD, Ravi Salgia, MD, PhD, Lecia V. Sequist, MD, Alice T. Shaw, MD, PhD, George R. Simon, MD, Neeta Somaiah, MD, David R. Spigel, MD, John Wrangle, MD, David Johnson, MD, Roy S. Herbst, MD, PhD, Paul Bunn, MD, Ramaswamy Govindan, MD  Journal of Thoracic Oncology  Volume 10, Issue 1, Pages S1-S63 (January 2015) DOI: /JTO Copyright © 2015 International Association for the Study of Lung Cancer Terms and Conditions

2 FIGURE 1 Potential targetable oncogenes by histology subtype. EGFR, epidermal growth factor receptor; ALK, anaplastic lymphoma kinase; DDR2, discoidin domain receptor tyrosine kinase 2; FGFR1, fibroblast growth factor receptor 1; KRAS, Kirsten rat sarcoma viral oncogene homolog; MET, MET proto-oncogene; PIK3CA, phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha; PTEN, phosphatase and tensin homology deleted on chromosome 10; RET, ret proto-oncogene; SCLC, small-cell lung cancer. Journal of Thoracic Oncology  , S1-S63DOI: ( /JTO ) Copyright © 2015 International Association for the Study of Lung Cancer Terms and Conditions

3 FIGURE 2 Chromatin-modifying enzymes. MEK, mitogen-activated protein kinase kinase; ERK, extracellular signal–regulated kinase; PHD, plant homeodomain; PI3K, phosphatidylinositol 3-kinase; PWWP, proline-tryptophan-tryptophan-proline. Journal of Thoracic Oncology  , S1-S63DOI: ( /JTO ) Copyright © 2015 International Association for the Study of Lung Cancer Terms and Conditions

4 FIGURE 3 ROS1, NTRK1, and RET inhibitors. MPRIP, myosin phosphatase Rho interacting protein; NTRK1, neurotrophic tyrosine kinase, receptor, type 1; EZR, ezrin; ROS, ROS proto-oncogene 1; AKT, v-akt murine thymoma viral oncogene homolog; KIF, kinesin family member 5B; and RET, ret proto-oncogene. Journal of Thoracic Oncology  , S1-S63DOI: ( /JTO ) Copyright © 2015 International Association for the Study of Lung Cancer Terms and Conditions

5 FIGURE 4 KRAS Mutations in NSCLC. ERK, extracellular signal-regulated kinase; GDP, guanosine 5’-diphosphate; GF, growth factor; GTP, guanosine 5’-triphosphate; JNK, Jun N-terminal kinase; MEK, MAP (mitogen-activated protein) kinase; PDK1, phosphoinositide-dependent kinase-1; PI3K, phosphatidylinositol 3-kinase; PKC, Protein kinase C; RAS, rat sarcoma; RTK, receptor tyrosine kinase; SOS, son of sevenless. Journal of Thoracic Oncology  , S1-S63DOI: ( /JTO ) Copyright © 2015 International Association for the Study of Lung Cancer Terms and Conditions

6 FIGURE 5 Mitotic/cyclin inhibitors. NHEJ, non-homologous end joining; HR, homologous recombination. Journal of Thoracic Oncology  , S1-S63DOI: ( /JTO ) Copyright © 2015 International Association for the Study of Lung Cancer Terms and Conditions

7 FIGURE 6 PARP inhibition: Mechanism of action (reproduced from Oncology Live, 2013, permission requested). BER, base excision repair; NAD, nicotinamide adenine dinucleotide; PARP, Poly(ADP-ribose) polymerase. Journal of Thoracic Oncology  , S1-S63DOI: ( /JTO ) Copyright © 2015 International Association for the Study of Lung Cancer Terms and Conditions

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