Medicine and Health Sciences Commons^™

A Genomically And Clinically Annotated Patient-Derived Xenograft Resource For Preclinical Research In Non-Small Cell Lung Cancer., Xing Yi Woo, Anuj Srivastava, Philip C Mack, Joel H. Graber, Brian J Sanderson, Michael W Lloyd, Mandy Chen, Sergii Domanskyi, Regina Gandour-Edwards, Rebekah A Tsai, James G. Keck, Mingshan Cheng, Margaret Bundy, Emily L Jocoy, Jonathan W Riess, William Holland, Stephen C. Grubb, James G Peterson, Grace Stafford, Carolyn Paisie, Steven Neuhauser, Radha Krishna Murthy Karuturi, Joshy George, Allen K. Simons, Margaret Chavaree, Clifford G Tepper, Neal Goodwin, Susan Airhart, Primo N Lara, Thomas H Openshaw, Edison Liu, David R Gandara, Carol J Bult

Faculty Research 2022

UNLABELLED: Patient-derived xenograft (PDX) models are an effective preclinical in vivo platform for testing the efficacy of novel drugs and drug combinations for cancer therapeutics. Here we describe a repository of 79 genomically and clinically annotated lung cancer PDXs available from The Jackson Laboratory that have been extensively characterized for histopathologic features, mutational profiles, gene expression, and copy-number aberrations. Most of the PDXs are models of non-small cell lung cancer (NSCLC), including 37 lung adenocarcinoma (LUAD) and 33 lung squamous cell carcinoma (LUSC) models. Other lung cancer models in the repository include four small cell carcinomas, two large cell neuroendocrine …

Proteogenomic Characterization Reveals Therapeutic Vulnerabilities In Lung Adenocarcinoma, Michael A. Gillette, Song Cao, Yize Li, Wen-Wei Liang, Michael C Wendl, Ramaswamy Govindan, Et Al.

2020-Current year OA Pubs

To explore the biology of lung adenocarcinoma (LUAD) and identify new therapeutic opportunities, we performed comprehensive proteogenomic characterization of 110 tumors and 101 matched normal adjacent tissues (NATs) incorporating genomics, epigenomics, deep-scale proteomics, phosphoproteomics, and acetylproteomics. Multi-omics clustering revealed four subgroups defined by key driver mutations, country, and gender. Proteomic and phosphoproteomic data illuminated biology downstream of copy number aberrations, somatic mutations, and fusions and identified therapeutic vulnerabilities associated with driver events involving KRAS, EGFR, and ALK. Immune subtyping revealed a complex landscape, reinforced the association of STK11 with immune-cold behavior, and underscored a potential immunosuppressive role of neutrophil degranulation. …

H3k9 Methyltransferases And Demethylases Control Lung Tumor-Propagating Cells And Lung Cancer Progression, S. P. Rowbotham, F Li, A. F. M. Dost, S. M. Louie, B. P. Marsh, P. Pessina, C. R. Anbarasu, Christine Fillmore Brainson, S. J. Tuminello, A. Lieberman, S. Ryeom, T. M. Schlaeger, B. J. Aronow, H. Watanabe, K. K. Wong, C. F. Kim

Toxicology and Cancer Biology Faculty Publications

Epigenetic regulators are attractive anticancer targets, but the promise of therapeutic strategies inhibiting some of these factors has not been proven in vivo or taken into account tumor cell heterogeneity. Here we show that the histone methyltransferase G9a, reported to be a therapeutic target in many cancers, is a suppressor of aggressive lung tumor-propagating cells (TPCs). Inhibition of G9a drives lung adenocarcinoma cells towards the TPC phenotype by de-repressing genes which regulate the extracellular matrix. Depletion of G9a during tumorigenesis enriches tumors in TPCs and accelerates disease progression metastasis. Depleting histone demethylases represses G9a-regulated genes and TPC phenotypes. Demethylase inhibition …

Large-Scale Association Analysis Identifies New Lung Cancer Susceptibility Loci And Heterogeneity In Genetic Susceptibility Across Histological Subtypes., James D Mckay, Rayjean J Hung, Younghun Han, Xuchen Zong, Robert Carreras-Torres, David C Christiani, Neil E Caporaso, Mattias Johansson, Xiangjun Xiao, Yafang Li, Jinyoung Byun, Alison Dunning, Karen A Pooley, David C Qian, Xuemei Ji, Geoffrey Liu, Maria N Timofeeva, Stig E Bojesen, Xifeng Wu, Loic Le Marchand, Demetrios Albanes, Heike Bickeböller, Melinda C Aldrich, William S Bush, Adonina Tardon, Gad Rennert, M Dawn Teare, John K Field, Lambertus A Kiemeney, Philip Lazarus, Aage Haugen, Stephen Lam, Matthew B Schabath, Angeline S Andrew, Hongbing Shen, Yun-Chul Hong, Jian-Min Yuan, Pier Alberto Bertazzi, Angela C Pesatori, Yuanqing Ye, Nancy Diao, Li Su, Ruyang Zhang, Yonathan Brhane, Natasha Leighl, Jakob S Johansen, Anders Mellemgaard, Walid Saliba, Christopher A Haiman, Lynne R Wilkens, Ana Fernandez-Somoano, Guillermo Fernandez-Tardon, Henricus F M Van Der Heijden, Jin Hee Kim, Juncheng Dai, Zhibin Hu, Michael P A Davies, Michael W Marcus, Hans Brunnström, Jonas Manjer, Olle Melander, David C Muller, Kim Overvad, Antonia Trichopoulou, Rosario Tumino, Jennifer A Doherty, Matt P Barnett, Chu Chen, Gary E Goodman, Angela Cox, Fiona Taylor, Penella Woll, Irene Brüske, H-Erich Wichmann, Judith Manz, Thomas R Muley, Angela Risch, Albert Rosenberger, Kjell Grankvist, Mikael Johansson, Frances A Shepherd, Ming-Sound Tsao, Susanne M Arnold, Eric B Haura, Ciprian Bolca, Ivana Holcatova, Vladimir Janout, Milica Kontic, Jolanta Lissowska, Anush Mukeria, Simona Ognjanovic, Tadeusz M Orlowski, Ghislaine Scelo, Beata Swiatkowska, David Zaridze, Per Bakke, Vidar Skaug, Shanbeh Zienolddiny, Eric J Duell, Lesley M Butler, Woon-Puay Koh, Yu-Tang Gao, Richard S Houlston, John Mclaughlin, Victoria L Stevens, Philippe Joubert, Maxime Lamontagne, David C Nickle, Ma'en Obeidat, Wim Timens, Bin Zhu, Lei Song, Linda Kachuri, María Soler Artigas, Martin D Tobin, Louise V Wain, Thorunn Rafnar, Thorgeir E Thorgeirsson, Gunnar W Reginsson, Kari Stefansson, Dana B Hancock, Laura J Bierut, Margaret R Spitz, Nathan C Gaddis, Sharon M Lutz, Fangyi Gu, Eric O Johnson, Ahsan Kamal, Claudio Pikielny, Dakai Zhu, Sara Lindströem, Xia Jiang, Rachel F Tyndale, Georgia Chenevix-Trench, Jonathan Beesley, Yohan Bossé, Stephen Chanock, Paul Brennan, Maria Teresa Landi, Christopher I Amos

Articles, Abstracts, and Reports

Although several lung cancer susceptibility loci have been identified, much of the heritability for lung cancer remains unexplained. Here 14,803 cases and 12,262 controls of European descent were genotyped on the OncoArray and combined with existing data for an aggregated genome-wide association study (GWAS) analysis of lung cancer in 29,266 cases and 56,450 controls. We identified 18 susceptibility loci achieving genome-wide significance, including 10 new loci. The new loci highlight the striking heterogeneity in genetic susceptibility across the histological subtypes of lung cancer, with four loci associated with lung cancer overall and six loci associated with lung adenocarcinoma. Gene expression …

The Distinct Metabolic Phenotype Of Lung Squamous Cell Carcinoma Defines Selective Vulnerability To Glycolytic Inhibition, Justin Goodwin, Michael L. Neugent, Shin Yup Lee, Joshua H. Choe, Hyunsung Choi, Dana M. R. Jenkins, Robin J. Ruthenborg, Maddox W. Robinson, Ji Yun Jeong, Masaki Wake, Hajime Abe, Norihiko Takeda, Hiroko Endo, Masahiro Inoue, Zhenyu Xuan, Hyuntae Yoo, Min Chen, Jung-Mo Ahn, John D. Minna, Kristi L. Helke, Pankaj K. Singh, David B. Shackelford, Jung-Whan Kim

Journal Articles: Eppley Institute

Adenocarcinoma (ADC) and squamous cell carcinoma (SqCC) are the two predominant subtypes of non-small cell lung cancer (NSCLC) and are distinct in their histological, molecular and clinical presentation. However, metabolic signatures specific to individual NSCLC subtypes remain unknown. Here, we perform an integrative analysis of human NSCLC tumour samples, patient-derived xenografts, murine model of NSCLC, NSCLC cell lines and The Cancer Genome Atlas (TCGA) and reveal a markedly elevated expression of the GLUT1 glucose transporter in lung SqCC, which augments glucose uptake and glycolytic flux. We show that a critical reliance on glycolysis renders lung SqCC vulnerable to glycolytic inhibition, …

Oncolog, Volume 41, Number 02, April-June 1996, Kathryn L. Hale, Stephanie P. Deming

OncoLog MD Anderson's Report to Physicians (All issues)

• lntraoperative lymphatic mapping elegant way to identify lymph node metastases in melanoma patients
• New Patient Referral Office changes with M. D. Anderson's referral policy
• Combined chemotherapy and radiation therapy bringing hope for inoperable lung cancer