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In This Issue

  • In This Issue
    In This Issue
    Cancer Discov December 1 2018 8 (12) 1494-1497; DOI:10.1158/2159-8290.CD-ITI8-12

In the Spotlight

Review

Research Briefs

  • Research Briefs | AuthorChoice
    Landscape of Acquired Resistance to Osimertinib in EGFR-Mutant NSCLC and Clinical Validation of Combined EGFR and RET Inhibition with Osimertinib and BLU-667 for Acquired RET Fusion
    Zofia Piotrowska, Hideko Isozaki, Jochen K. Lennerz, Justin F. Gainor, Inga T. Lennes, Viola W. Zhu, Nicolas Marcoux, Mandeep K. Banwait, Subba R. Digumarthy, Wenjia Su, Satoshi Yoda, Amanda K. Riley, Varuna Nangia, Jessica J. Lin, Rebecca J. Nagy, Richard B. Lanman, Dora Dias-Santagata, Mari Mino-Kenudson, A. John Iafrate, Rebecca S. Heist, Alice T. Shaw, Erica K. Evans, Corinne Clifford, Sai-Hong I. Ou, Beni Wolf, Aaron N. Hata and Lecia V. Sequist
    Cancer Discov December 1 2018 8 (12) 1529-1539; DOI:10.1158/2159-8290.CD-18-1022

    RET fusions were detected in patients with EGFR-mutant NSCLC who developed resistance to EGFR inhibition, and targeting RET in combination with EGFR inhibition produced responses in two patients.

  • Research Briefs | AuthorChoice
    Isoform Switching as a Mechanism of Acquired Resistance to Mutant Isocitrate Dehydrogenase Inhibition
    James J. Harding, Maeve A. Lowery, Alan H. Shih, Juan M. Schvartzman, Shengqi Hou, Christopher Famulare, Minal Patel, Mikhail Roshal, Richard K. Do, Ahmet Zehir, Daoqi You, S. Duygu Selcuklu, Agnes Viale, Martin S. Tallman, David M. Hyman, Ed Reznik, Lydia W.S. Finley, Elli Papaemmanuil, Alessandra Tosolini, Mark G. Frattini, Kyle J. MacBeth, Guowen Liu, Bin Fan, Sung Choe, Bin Wu, Yelena Y. Janjigian, Ingo K. Mellinghoff, Luis A. Diaz, Ross L. Levine, Ghassan K. Abou-Alfa, Eytan M. Stein and Andrew M. Intlekofer
    Cancer Discov December 1 2018 8 (12) 1540-1547; DOI:10.1158/2159-8290.CD-18-0877

    IDH1- or IDH2-mutant acute myeloid leukemia and solid tumors can develop resistance to isoform-selective IDH inhibition through mutation of the other IDH isoform.

Research Articles

  • Research Articles | AuthorChoice
    Integrative Molecular Characterization of Malignant Pleural Mesothelioma
    Julija Hmeljak, Francisco Sanchez-Vega, Katherine A. Hoadley, Juliann Shih, Chip Stewart, David Heiman, Patrick Tarpey, Ludmila Danilova, Esther Drill, Ewan A. Gibb, Reanne Bowlby, Rupa Kanchi, Hatice U. Osmanbeyoglu, Yoshitaka Sekido, Jumpei Takeshita, Yulia Newton, Kiley Graim, Manaswi Gupta, Carl M. Gay, Lixia Diao, David L. Gibbs, Vesteinn Thorsson, Lisa Iype, Havish Kantheti, David T. Severson, Gloria Ravegnini, Patrice Desmeules, Achim A. Jungbluth, William D. Travis, Sanja Dacic, Lucian R. Chirieac, Françoise Galateau-Sallé, Junya Fujimoto, Aliya N. Husain, Henrique C. Silveira, Valerie W. Rusch, Robert C. Rintoul, Harvey Pass, Hedy Kindler, Marjorie G. Zauderer, David J. Kwiatkowski, Raphael Bueno, Anne S. Tsao, Jenette Creaney, Tara Lichtenberg, Kristen Leraas, Jay Bowen, TCGA Research Network, Ina Felau, Jean Claude Zenklusen, Rehan Akbani, Andrew D. Cherniack, Lauren A. Byers, Michael S. Noble, Jonathan A. Fletcher, A. Gordon Robertson, Ronglai Shen, Hiroyuki Aburatani, Bruce W. Robinson, Peter Campbell and Marc Ladanyi
    Cancer Discov December 1 2018 8 (12) 1548-1565; DOI:10.1158/2159-8290.CD-18-0804

    Comprehensive, multiplatform genomic analyses of malignant pleural mesothelioma characterize a near-haploid molecular subtype, define prognostic molecular subsets, and identify high expression of VISTA in the epithelioid subtype.

  • Research Articles | AuthorChoice
    A Novel MCL1 Inhibitor Combined with Venetoclax Rescues Venetoclax-Resistant Acute Myelogenous Leukemia
    Haley E. Ramsey, Melissa A. Fischer, Taekyu Lee, Agnieszka E. Gorska, Maria Pia Arrate, Londa Fuller, Kelli L. Boyd, Stephen A. Strickland, John Sensintaffar, Leah J. Hogdal, Gregory D. Ayers, Edward T. Olejniczak, Stephen W. Fesik and Michael R. Savona
    Cancer Discov December 1 2018 8 (12) 1566-1581; DOI:10.1158/2159-8290.CD-18-0140

    An identified MCL1 inhibitor induced apoptosis in AML cells and was safely combined with BCL2 inhibition to overcome BCL2 inhibitor resistance and enhance antitumor activity in mouse models of AML.

  • Research Articles | AuthorChoice
    AMG 176, a Selective MCL1 Inhibitor, Is Effective in Hematologic Cancer Models Alone and in Combination with Established Therapies
    Sean Caenepeel, Sean P. Brown, Brian Belmontes, Gordon Moody, Kathleen S. Keegan, Danny Chui, Douglas A. Whittington, Xin Huang, Leszek Poppe, Alan C. Cheng, Mario Cardozo, Jonathan Houze, Yunxiao Li, Brian Lucas, Nick A. Paras, Xianghong Wang, Joshua P. Taygerly, Marc Vimolratana, Manuel Zancanella, Liusheng Zhu, Elaina Cajulis, Tao Osgood, Jan Sun, Leah Damon, Regina K. Egan, Patricia Greninger, Joseph D. McClanaghan, Jianan Gong, Donia Moujalled, Giovanna Pomilio, Pedro Beltran, Cyril H. Benes, Andrew W. Roberts, David C. Huang, Andrew Wei, Jude Canon, Angela Coxon and Paul E. Hughes
    Cancer Discov December 1 2018 8 (12) 1582-1597; DOI:10.1158/2159-8290.CD-18-0387

    Drug discovery and optimization yielded the selective MCL1 inhibitor AMG 176, which induced apoptosis in cells from hematologic malignancies in vitro and in vivo and could be combined with other therapies.

  • Research Articles
    Exploiting MCL1 Dependency with Combination MEK + MCL1 Inhibitors Leads to Induction of Apoptosis and Tumor Regression in KRAS-Mutant Non–Small Cell Lung Cancer
    Varuna Nangia, Faria M. Siddiqui, Sean Caenepeel, Daria Timonina, Samantha J. Bilton, Nicole Phan, Maria Gomez-Caraballo, Hannah L. Archibald, Chendi Li, Cameron Fraser, Diamanda Rigas, Kristof Vajda, Lorin A. Ferris, Michael Lanuti, Cameron D. Wright, Kevin A. Raskin, Daniel P. Cahill, John H. Shin, Colleen Keyes, Lecia V. Sequist, Zofia Piotrowska, Anna F. Farago, Christopher G. Azzoli, Justin F. Gainor, Kristopher A. Sarosiek, Sean P. Brown, Angela Coxon, Cyril H. Benes, Paul E. Hughes and Aaron N. Hata
    Cancer Discov December 1 2018 8 (12) 1598-1613; DOI:10.1158/2159-8290.CD-18-0277

    Dual inhibition of MCL1 and MEK induces apoptosis and tumor regression in KRAS-mutant models of NSCLC, and BCL-xL inhibition may enhance sensitivity to MCL1 inhibition.

  • Research Articles
    Deletion 6q Drives T-cell Leukemia Progression by Ribosome Modulation
    Stéphanie Gachet, Tiama El-Chaar, David Avran, Eulalia Genesca, Frédéric Catez, Samuel Quentin, Marc Delord, Gabriel Thérizols, Delphine Briot, Godelieve Meunier, Lucie Hernandez, Marika Pla, Willem K. Smits, Jessica G. Buijs-Gladdines, Wouter Van Loocke, Gerben Menschaert, Isabelle André-Schmutz, Tom Taghon, Pieter Van Vlierberghe, Jules P. Meijerink, André Baruchel, Hervé Dombret, Emmanuelle Clappier, Jean-Jacques Diaz, Claude Gazin, Hugues de Thé, François Sigaux and Jean Soulier
    Cancer Discov December 1 2018 8 (12) 1614-1631; DOI:10.1158/2159-8290.CD-17-0831

    SYNCRIP and SNHG5 haploinsufficiency increases leukemic-initiating cell activity and drives del(6q) T-ALL progression by reducing the translation efficiency of transcripts involved in mitochondrial respiration.

  • Research Articles
    TET2 Deficiency Causes Germinal Center Hyperplasia, Impairs Plasma Cell Differentiation, and Promotes B-cell Lymphomagenesis
    Pilar M. Dominguez, Hussein Ghamlouch, Wojciech Rosikiewicz, Parveen Kumar, Wendy Béguelin, Lorena Fontán, Martín A. Rivas, Patrycja Pawlikowska, Marine Armand, Enguerran Mouly, Miguel Torres-Martin, Ashley S. Doane, María T. Calvo Fernandez, Matt Durant, Veronique Della-Valle, Matt Teater, Luisa Cimmino, Nathalie Droin, Saber Tadros, Samaneh Motanagh, Alan H. Shih, Mark A. Rubin, Wayne Tam, Iannis Aifantis, Ross L. Levine, Olivier Elemento, Giorgio Inghirami, Michael R. Green, Maria E. Figueroa, Olivier A. Bernard, Said Aoufouchi, Sheng Li, Rita Shaknovich and Ari M. Melnick
    Cancer Discov December 1 2018 8 (12) 1632-1653; DOI:10.1158/2159-8290.CD-18-0657

    Somatic loss-of-function mutation of TET2 reduces enhancer hydroxymethylation to suppress genes that promote exit of B-cells from germinal centers and is a driving event in DLBCL.

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