Therapeutic Targeting and Monitoring Tumor Microenvironments   Terrace Ballroom IV (400 Level), Pennsylvania Convention Center

Methods Workshop

Systems Approaches to Cancer   Room 121, Pennsylvania Convention Center

Educational Session

From Chemistry to the Clinic: Pathways for Drug Discovery and Development, Part 1: Optimizing Drug Discovery: Insights on an Important Process   Room 113, Pennsylvania Convention CenterTumor Immunology and Immunotherapy for the Non-Immunologist   Grand Ballroom (300 Level), Pennsylvania Convention Center

Saturday, 10:15 AM - 12:15 PM

Educational Session

Bench to Bedside and Back Again: Biology and Therapy of ALK and BRAF Cancers   Room 115, Pennsylvania Convention CenterComputational and Functional Modeling of Hot Big Data   Room 204, Pennsylvania Convention Center

Methods Workshop

How and When to Use Chemical Probes   Room 118, Pennsylvania Convention Center

Educational Session

Pediatric Low Grade Gliomas: Silent But Still Deadly   Room 114, Pennsylvania Convention Center

Methods Workshop

Large Scale Functional Genomic Screens: In Need of Controls?   Grand Ballroom (300 Level), Pennsylvania Convention Center

Saturday, 1:00 PM - 3:00 PM

Educational Session

Mechanisms of Cancer Therapy Resistance   Room 204, Pennsylvania Convention CenterRole of Non-Coding RNAs in Cancer   Terrace Ballroom IV (400 Level), Pennsylvania Convention CenterChemical Biology and Molecular Pharmacology   Room 103, Pennsylvania Convention CenterTumor Heterogeneity and Evolution   Terrace Ballroom II-III (400 Level), Pennsylvania Convention Center

Methods Workshop

Cell Line Authentication: Improving the Reproducibility and Translatability of Preclinical Cancer Research   Room 108, Pennsylvania Convention CenterDesign and Method Workshop for Clinical Trials and Population Studies, Part 3: Challenges of Genomics, Integromics, and Tumor Heterogeneity in Clinical Trial Designs   Room 201, Pennsylvania Convention Center

Saturday, 3:15 PM - 5:15 PM

Educational Session

Translating Insights from Mouse Cancer Models to Therapeutic Targeting   Room 114, Pennsylvania Convention CenterEndogenous Steroid Hormones and Risk of Cancer   Room 120, Pennsylvania Convention CenterTherapeutic Targeting the Diverse Immune Inhibitory Pathways in the Tumor Microenvironment   Terrace Ballroom II-III (400 Level), Pennsylvania Convention Center

Apr 19

Sunday, 7:00 AM - 8:00 AM

Meet-the-Expert Session

Unraveling Hormone Dependence in Cancer   Room 119, Pennsylvania Convention CenterNovel Therapeutic Targets in Myeloma   Room 113, Pennsylvania Convention CenterThe Biologic Signature of Melanoma to Guide Therapy   Room 120, Pennsylvania Convention CenterThe Promise of Personalized Medicine   Room 201, Pennsylvania Convention Center

Sunday, 9:30 AM - 12:00 PM

Plenary Session

Opening Plenary: The Genome and Beyond   Hall A (200 Level), Pennsylvania Convention Center

Sunday, 1:00 PM - 5:00 PM

Poster Session

Therapeutic Resistance in Lung Cancer   Section 31

Therapeutic Resistance in Hormone-Sensitive Cancers

Tyrosine Kinase and Phosphatase Inhibitors   Section 32

Signal Transduction Inhibitors   Section 28Kinases and Inhibitors   Section 6Cell Adhesion and Extracellular Matrix   Section 15Tumor- and Blood-based Genotyping   Section 26Targeting Signal Transduction   Section 29

Predictive Biomarkers: Lung and Gastrointestinal Cancers   Section 24Crosstalk of the Microenvironment and the Tumor Clone   Section 17Cell Signaling in Cancer 1   Section 2Histone Methylation and Acetylation   Section 5Long Non-Coding RNAs   Section 7Cell Death Mechanisms   Section 13D Cultures and Tissue/Organoid Models   Section 14Immune Checkpoints   Section 12MicroRNA Regulation of Cancer Biology   Section 8Carcinogenic Mechanisms 1   Section 34Signaling Axes Regulating Motility and Invasion   Section 21New Insights from Imaging and Cell Isolation   Section 9Modeling Cancer Prevention   Section 37

Late-Breaking Poster Session

Late-Breaking Research: Experimental and Molecular Therapeutics 1   Section 39Late-Breaking Research: Molecular and Cellular Biology 1   Section 41

Poster Session

Pediatric Cancer: Basic Science 1   Section 20

Circulating Tumor Cells and Disseminated Tumor Cells  

Section 16Deregulation of Gene Expression in Prostate Cancer and Sarcoma   Section 4

Sunday, 1:00 PM - 3:00 PM

Drug Development Track: Special Session

New Drugs on the Horizon 1   Room 204, Pennsylvania Convention Center

Sunday, 1:00 PM - 5:00 PM

Poster Session

Computational Tools / Genomic Profiling of Tumors   Section 3Prognostic and Toxicity Biomarkers   Section 25Diagnostic Biomarkers   Section 23

Sunday, 1:00 PM - 3:00 PM

Major Symposium

Autophagy and Cancer   Room 115, Pennsylvania Convention Center

Sunday, 1:00 PM - 5:00 PM

Poster Session

Non-Coding RNAs in Cancer Biology 1   Section 10Cytokines and Chemokines and the Microenvironment   Section 18Tumor Microenvironment/Innate Immune Activators   Section 13

Sunday, 3:00 PM - 5:00 PM

Regulatory Science and Policy Session

Evolution of Personalized Drug Development in Oncology-Kinase Inhibitors   Room 119, Pennsylvania Convention Center

Sunday, 3:15 PM - 5:15 PM

Late-Breaking Minisymposium

Minisymposium: Late-Breaking Research   Room 122, Pennsylvania Convention Center

Minisymposium

Signaling of the Microenvironment Regulates Tumor Progression   Room 113, Pennsylvania Convention CenterOncogenic Signaling and Cell Death   Room 121, Pennsylvania Convention CenterLiquid Biopsies   Terrace Ballroom I (400 Level), Pennsylvania Convention CenterBiomarkers and Cancer: New Insights   Terrace Ballroom IV (400 Level), Pennsylvania Convention CenterCell Cycle Mechanisms of Anticancer Drug Action   Room 120, Pennsylvania Convention CenterDrug Discovery: New Targets and Antibody Drug Conjugates   Room 201, Pennsylvania Convention CenterCancer Stem Cells 1   Room 115, Pennsylvania Convention Center

Clinical Trials Minisymposium

Clinical Trials Minisymposium   Room 103, Pennsylvania Convention Center

Sunday, 3:15 PM - 5:30 PM

Minisymposium

Cancer Genomics: Characterization, Evolution, and Function   Room 114, Pennsylvania Convention Center

Sunday, 3:15 PM - 5:15 PM

Drug Development Track: Special Session

New Drugs on the Horizon 2   Room 204, Pennsylvania Convention Center

Sunday, 5:30 PM - 6:30 PM

Awards and Lectures

Presidential Address   Hall A (200 Level), Pennsylvania Convention Center

Apr 20

Monday, 7:00 AM - 8:00 AM

Meet-the-Expert Session

Molecular Pathology in Oncology   Room 114, Pennsylvania Convention Center

Examination of Cancer Pathways Using Computational Approaches   Section 4

Monday, 8:00 AM - 12:00 PM

Poster Session

Angiogenesis Inhibitors   Section 14Pediatric Cancer: Clinical Investigations / Regulatory Science and Policy   Section 24Cell Death and Survival   Section 1

In Vitro and In Vivo Models and New Targets   Section 30Inhibitors of UPS and HSP90 Pathways and Other Targets   Section 31Cell Cycle, DNA, and Transcription Targets   Section 28Human-in-Mouse Models of Cancer 1   Section 17Epithelial-Mesenchymal Transition, Mesenchymal-Epithelial Transition, and Related Behaviors   Section 16Unfolded Protein Response and Oxidative Stress   Section 10Novel Agents and Mechanisms of Action   Section 32Molecular Endocrinology of Cancer 1   Section 36Cell Signaling in Cancer 2   Section 2

Metabolic Pathways and Signaling Pathways That Regulate Metabolism

Monday, 1:00 PM - 5:00 PM

Poster Session

Resistance to Pathway-Targeted Therapeutics 1   Section 33

Session Title: Cell Signaling in Cancer 3Session Type: Poster SessionSession Start/End Time:

Monday, Apr 20, 2015, 1:00 PM - 5:00 PM

Location: Section 3CME: (not eligible for CME credit)Session Category:

Molecular and Cellular Biology

1967: Elucidation of signaling pathways that mediate gastrin-induced JNK activation and pGSK3β/Snail induction in gastric cancer

Monday, Apr 20, 2015, 1:00 PM - 5:00 PM, Goutam Sondarva 2 , Sreevidya Santha 1 , Ajay Rana 2 , Basabi

Department of Medicine, Division of Gastroenterology & Nutrition, Loyola University Chicago, Maywood, IL; 2 Department of Pharmacology and Experimental Therapeutics, Loyola University Chicago, Maywood, IL

1968: Activation of AKT negatively regulates the pro-apoptotic function of death-associated protein kinase 3 (DAPK3) in prostate cancerMonday, Apr 20, 2015, 1:00 PM - 5:00 PMTrinath P. Das 1 , Arokya MS Papu John 1 , Ram V. Roy 2 , Sandhya R. Rao 3 , Houda Alatassi 3 , Chendil Damodaran 1 , Murali M. Ankhem 4 . 1 Clinical and tranlational research, University of Louisville, Louisville, KY; 2 University of Kentucky, Lexington, KY; 3 University of Louisville, Louisville, KY; 4 University of Louisville School of Medicine, Louisville, KY

1969: Regulation of cell cycle progression in BRAFV600E inhibitor-resistant human melanoma by histone deacetylase inhibitorMonday, Apr 20, 2015, 1:00 PM - 5:00 PMAntoni X. Toresss-Collado, Ramin Nazarian, Ali R. Jazirehi. UCLA David Geffen School of Medicine, Los Angeles, CA

1940: Dual inhibition of mTORC1/C2 and HER2 results in maximal antitumor efficacy in preclinical model of HER2+ breast cancer resistant to trastuzumab therapyMonday, Apr 20, 2015, 1:00 PM - 5:00 PMPradip Kr De, Yuliang Sun, Jennifer H. Carlson, Xiaoqian Lin, Nandini Dey, Brian Leyland-Jones. Avera Research Institute, Sioux Falls, SD

Session Title: Targeting Pathway Rewiring to Improve Cancer TherapySession Type: Major SymposiumSession Start/End Time: Monday, Apr 20, 2015, 1:00 PM - 3:00 PMLocation: Room 103, Pennsylvania Convention CenterCME: CME-DesignatedCME/CE Hours: 2Session Description: Both the emergence of malignant cells, and their subsequent resistance

to killing by molecularly targeted and cytotoxic therapies arises from re-wiring of signaling pathways that control cell growth, proliferation, invasion, and programmed cell death. This session will review how the continual ability of cancer cells to re-wire signaling pathways leads to the emergence of therapeutic resistance, both through tumor cell autonomous changes and through tumor cell manipulation of the local microenvironment. Presenters will then demonstrate how a detailed

molecular understanding of this process can lead to novel therapeutic strategies that can kill these resistant clones and/or prevent their emergence. Finally, this session will show how the inherent plasticity of signaling pathways in cancer can also be taken advantage of therapeutically in order to make tumor cells sensitive to drugs that they were not previously sensitive to, through a process called “therapeutic dynamic re-wiring”

Presentations:ChairpersonMonday, Apr 20, 2015, 1:00 PM - 3:00 PMMichael B. Yaffe . MIT Koch Institute for Integrated Cancer Research, Cambridge, MA Introduction

Monday, Apr 20, 2015, 1:00 PM - 1:10 PM

SY19-01: Therapeutic network re-wiring of the DNA damage response can be used to enhance tumor killing by cytotoxic chemotherapyMonday, Apr 20, 2015, 1:10 PM - 1:30 PMMichael J. Lee , Yogesh Dayma , Anne-Margriet Heijinks , Stephen W. Morton , Erik C. Dreaden , Paula T. Hammond , Michael B. Yaffe . MIT Koch Institute for Integrated Cancer Research, Cambridge, MA, MIT Koch Institute for Integrated Cancer Research, Cambridge, MADiscussion

Monday, Apr 20, 2015, 1:30 PM - 1:35 PM

Cancer cell-state plasticity and resistance to therapyMonday, Apr 20, 2015, 1:35 PM - 1:55 PMRafaella Sordella . Cold Spring Harbor Laboratory, Cold Spring Harbor, NY Discussion

Monday, Apr 20, 2015, 1:55 PM - 2:00 PM

SY19-03: Rewiring of signaling associated protein complexes in cancerMonday, Apr 20, 2015, 2:00 PM - 2:20 PMEric B. Haura . Moffitt Cancer Center & Research Institute, Tampa, FL Discussion

Monday, Apr 20, 2015, 2:20 PM - 2:25 PM

Resiliency of the kinome to targeted kinase inhibitors: Strategies to block rewiringMonday, Apr 20, 2015, 2:25 PM - 2:45 PMGary L. Johnson . University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC

Session Title: Molecular Mechanisms of Sensitivity or Resistance to Pathway-Targeted Agents

Session Type: MinisymposiumSession Start/End Time: Monday, Apr 20, 2015, 3:00 PM - 5:00 PMLocation: Room 118, Pennsylvania Convention CenterCME: CME-DesignatedCME/CE Hours: 2Session Category: Experimental and Molecular TherapeuticsPresentations:

Chairperson

Monday, Apr 20, 2015, 3:00 PM - 5:00 PMPaul Workman . The Institute of Cancer Research, London, United Kingdom Chairperson

Monday, Apr 20, 2015, 3:00 PM - 3:05 PMRichard M. Marais . Cancer Research UK Manchester Institute, Manchester, United KingdomIntroduction

Monday, Apr 20, 2015, 3:00 PM - 3:05 PM

2841: A co-clinical assessment of patterns of BRAF inhibitor resistanceMonday, Apr 20, 2015, 3:05 PM - 3:20 PMLawrence N. Kwong 1 , Genevieve Boland 1 , Dennie Frederick 2 , Timothy Helms 1 , Ahmad Akid 1 , John Miller 1 , Shan Jiang 1 , Zachary Cooper 1 , Xingzhi Song 1 , Sahil Seth 1 , Jennifer Kamara 1 , Alexei Protopopov 1 , Gordon Mills 1 , Keith Flaherty 2 , Jennifer Wargo 1 , Lynda Chin 1 . 1 UT MD Anderson Cancer Center, Houston, TX; 2 Massachusetts General Hospital, Boston, MA2842: Personalized pre-clinical trials in BRAF inhibitor resistant patient derived xenograft models of melanoma identify c-Met as an effective second line combination therapy targetMonday, Apr 20, 2015, 3:20 PM - 3:35 PMClemens Krepler 1 , Min Xiao 1 , Katrin Sproesser 1 , Patricia Brafford 1 , Batool Shannan 1 , Marilda Beqiri 1 , Wei Xu 2 , Bradley Garman 2 , Katherine L. Nathanson 2 , Xiaowei Xu 2 , Giorgos Karakousis 2 , Gordon B. Mills 3 , Yiling Lu 3 , Giordano Caponigro 4 , Markus Boehm 4 , Malte Peters 4 , Lynn Schuchter 2 , Meenhard Herlyn 1 . 1 The Wistar Institute, Philadelphia, PA; 2 University of Pennsylvania Abramson Cancer Center, Philadelphia, PA; 3 University of Texas MD Anderson Cancer Center, Huston, TX; 4 Novartis Oncology Translational Medicine, Cambridge, MA2843: Resistance to ERK inhibitors as a result of an acquired novel P-loop mutation of ERK2Monday, Apr 20, 2015, 3:35 PM - 3:50 PMPaul A. Clarke, Toby Roe, Kate Swabey, Craig McAndrew, Kathy Boxall, Isaac

Westwood, Robert van Montfort, Bissan Al-Lazikhani, Paul Workman. Cancer Research UK Cancer Therapeutics Unit, Institute of Cancer Research, London, United Kingdom2844: RNA interference kinome-wide screen reveals a role for PDK1 in acquired resistance to CDK4/6 inhibition ER-positive breast cancerMonday, Apr 20, 2015, 3:50 PM - 4:05 PMValerie M. Jansen, Neil E. Bhola, Joshua A. Bauer, Carlos L. Arteaga. Vanderbilt, Nashville, TN2845: Co-acquisition of T790M and EMT in resistant EGFR mutant non-small cell lung cancer can be overcome by combined irreversible EGFR and BCL-XL inhibitionMonday, Apr 20, 2015, 4:05 PM - 4:20 PMAaron N. Hata 1 , Matthew J. Niederst 1 , Hannah L. Archibald 1 , Hillary Mulvey 1 , Jungoh Ham 2 , Maria Gomez-Caraballo 1 , Anuj Kalsy 1 , Anthony C. Faber 2 , Jeffrey Engelman 1 . 1 Massachusetts General Hospital, Boston, MA; 2 Virginia Commonwealth University, Richmond, VA2846: Ultrasensitive detection of actionable subclones in chronic myeloid leukemiaMonday, Apr 20, 2015, 4:20 PM - 4:35 PMMichael W. Schmitt, Bella Aminov, Jerald P. Radich, Lawrence A. Loeb. University of Washington, Seattle, WA2847: High complexity barcoding to study clonal dynamics in response to cancer therapyMonday, Apr 20, 2015, 4:35 PM - 4:50 PMHyo-eun C. Bhang 1 , David A. Ruddy 1 , Viveksagar Krishnamurthy Radhakrishna 1 , Rui Zhao 2 , Iris Kao 1 , Daniel Rakiec 1 , Pamela Shaw 1 , Marissa Balak 1 , Justina X. Caushi 1 , Elizabeth Ackley 1 , Nicholas Keen 1 , Michael R. Schlabach 1 , Michael Palmer 1 , William R. Sellers 1 , Franziska Michor 2 , Vesselina G. Cooke 1 , Joshua M. Korn 1 , Frank Stegmeier 1 . 1 Novartis Institutes for BioMedical Research, Cambridge, MA; 2 Dana-Farber Cancer Institute, Boston, MA

Session Title: Resistance to Pathway-Targeted Therapeutics 2Session Type: Poster SessionSession Start/End Time: Tuesday, Apr 21, 2015, 8:00 AM -12:00 PMLocation: Section 31CME: (not eligible for CME credit)Session Category: Experimental and Molecular TherapeuticsPresentations:

3578: Dual mTOR kinase inhibitor overcomes rapamycin resistance in vitroTuesday, Apr 21, 2015, 8:00 AM -12:00 PMYao Dai 1 , Li Zhao 2 , Dietmar Siemann 1 . 1 University of Florida, Gainesville, FL; 2 China Pharmaceutical University, Nanjing, China3579: Identification of biomarkers of AXL-mediated drug resistance in head and neck squamous cell carcinomaTuesday, Apr 21, 2015, 8:00 AM -12:00 PMKavitha Balaji 1 , Robert Cardnell 2 , Lixia Diao 3 , Pan Tong 3 , Milena Mak 2 , You Hong Fan 2 , Fatemeh Masrorpour 2 , Steven L. Warner 4 , David J. Bearss 4 , Ignacio Wistuba 5 , Gordon B. Mills 6 , John Heymach 2 , Khandan Keyomarsi 1 , Jing Wang 3 , Lauren Averett Byers 2 .

1 Department of Experimental Radiation Oncology, MD Anderson Cancer Center, Houston, TX; 2 Department of Thoracic/Head and Neck Medical Oncology, MD Anderson Cancer Center, Houston, TX; 3 Department of Bioinformatics and Computational Biology, MD Anderson Cancer Center, Houston, TX; 4 Tolero Pharmaceutical, Inc., Lehi, UT; 5 Department of Translational Molecular Pathology, MD Anderson Cancer Center, Houston, TX; 6 Department of Systems Biology, MD Anderson Cancer Center, Houston, TX 3580: Downregulated miR-30a promotes acquisition of chemoresistance by targeting endothelin A receptor in ovarian carcinomaTuesday, Apr 21, 2015, 8:00 AM -12:00 PMRosanna Sestito 1 , Roberta Cianfrocca 1 , Laura Rosanò 1 , Elisa Semprucci 1 , Piera Tocci 1 , Valeriana Di Castro 1 , Gabriella Ferrandina 2 , Anna Bagnato 1 . 1 Regina Elena National Cancer Inst., Rome, Italy; 2 Gynecologic Oncology Unit, Catholic University of Rome, Rome, Italy 3581: Rapid conversion to resistance, of a colon PDX with ret-fusion, by ponatinib treatment could potentially be attributed to the introduction of the gate keeper mutation V804MTuesday, Apr 21, 2015, 8:00 AM -12:00 PMMengmeng Yang, Jie Cai, Sheng Guo, Jean-Pierre Wery, Henry Qixiang Li. Crown Bioscience, Inc., Santa Clara, CA3582: Epidermal growth factor receptor and anaplastic lymphoma kinase bypass signaling in oral squamous cell carcinoma in vivo Tuesday, Apr 21, 2015, 8:00 AM -12:00 PMCara B. Gonzales 1 , Heping Chen 1 , Jorge J. De La Chapa 1 , Nameer B. Kirma 2 . 1 UTHSCSA Dental School, San Antonio, TX; 2 UTHSCSA Medical School, San Antonio, TX 3583: Drug-resistant NPM/ALK mutants show different sensitivity to second generation tyrosine kinase inhibitorsTuesday, Apr 21, 2015, 8:00 AM -12:00 PMLuca Mologni, Monica Ceccon, Diletta Fontana, Alessandra Pirola, Rocco Piazza, Carlo Gambacorti-Passerini. University of Milano-Bicocca, Monza, Italy3584: Lysine specific demethylase 1 inhibition attenuates enzalutamide resistant androgen receptor V7 splice variant activationTuesday, Apr 21, 2015, 8:00 AM -12:00 PMSergio Regufe da Mota, Sarah Bailey, Rosemary A. Strivens, Annette L. Hayden, Graham Packham, Simon J. Crabb. University of Southampton, Southampton, United Kingdom3585: HER3 and IGF1R are major mediators of both acquired and intrinsic cetuximab resistance in head and neck squamous cell carcinomasTuesday, Apr 21, 2015, 8:00 AM -12:00 PMIda Kjaer 1 , Trine Lindsted 1 , Camilla Fröhlich 1 , Ivan D. Horak 1 , Michael Kragh 1 , Jesper V. Olsen 2 , Mikkel W. Pedersen 1 . 1 Symphogen A/S, Ballerup, Denmark; 2 The Novo Nordisk Foundation Center for Protein Reasearch Faculty of Health and Medical Sciences University of Copenhagen, Copenhagen, Denmark3586: The use of kinome profiling to determine potential resistance pathways in pancreatic cancer cells treated with PIM kinase inhibitorsTuesday, Apr 21, 2015, 8:00 AM -12:00 PMVandana Singh 1 , Brittany Nixon 1 , T.S. Karim Gilbert 2 , Steve Warner 3 , David Bearss 3 , Lee M. Graves 2 , Antonio T. Baines 1 . 1 North Carolina Central University, Durham, NC;

2 University of North Carolina-Chapel Hill, Chapel Hill, NC; 3 Tolero Pharmaceuticals, Salt Lake City, UT3587: Developing targeted therapy for the treatment of drug-resistant ovarian cancerTuesday, Apr 21, 2015, 8:00 AM -12:00 PMKelly M. Kreitzburg 1 , Zacchary Dobbins 1 , Ashwini Katre 1 , Tooba Anwer 1 , Ronald Alvarez 1 , Charles N. Landen 2 , Karina J. Yoon 1 . 1 University of Alabama at Birmingham, Birmingham, AL; 2 University of Virginia, Charlottesville, VA 3588: Emergence of multiple EGFR extracellular mutations during cetuximab treatment in colorectal cancerTuesday, Apr 21, 2015, 8:00 AM -12:00 PMLuca Lazzari 1 , Sabrina Arena 1 , Beatriz Bellosillo 2 , Giulia Siravegna 1 , Alejandro Martínez 2 , Israel Cañadas 2 , Noelia Ferruz 3 , Mariangela Russo 1 , Sandra Misale 1 , Iria González 2 , Mar Iglesias 2 , Elena Gavilan 2 , Giorgio Corti 1 , Sebastijan Hobor 1 , Giovanni Crisafulli 1 , Marta Salido 2 , Juan Sánchez 2 , Alba Dalmases 2 , Joaquim Bellmunt 2 , Gianni De Fabritiis 3 , Ana Rovira 2 , Federica Di Nicolantonio 1 , Joan Albanell 2 , Alberto Bardelli 1 , Clara Montagut 2 . 1 Candiolo Cancer Center, FPO-IRCCS, Candiolo (Torino), Italy; 2 Hospital del Mar, Barcelona, Spain; 3 Computational Biophysics Laboratory (GRIB-IMIM), Pompeu Fabra University, PRBB, Barcelona, Spain3589: Validation of the role of circulating tumor DNA (ctDNA) in tracking mechanisms of resistance to anti-EGFR monoclonal antibodies (AE-mABs): preliminary results of the PROSPECT-C prospective trialTuesday, Apr 21, 2015, 8:00 AM -12:00 PMKhurum Khan 1 , George Vlachogianis 2 , David Cunningham 1 , Jens Hahne 2 , Mahnaz Darvish- Damavandi 2 , Sarah Barton 2 , Francesco Trevisani 2 , Giulia Mentrast 2 , Clare Peckitt 2 , Andrea Lampis 2 , Chiara Braconi 2 , Nasir Khan 2 , Ruwaida Begum 1 , Naureen Starling 1 , Sheela Rao 3 , David Watkins 1 , Annette Bryant 1 , Ian Chau 1 , Nicola Valeri 2 . 1 The Royal Marsden NHS Foundation Trust, Sutton, Surrey, United Kingdom; 2 The Institute of Cancer Research, Sutton, Surrey, United Kingdom; 3 the Royal Marsden NHS Foundation Trust, Sutton, Surrey, United Kingdom3590: Resistance mechanisms to ALK inhibitorsTuesday, Apr 21, 2015, 8:00 AM -12:00 PMRyohei Katayama 1 , Noriko Yanagitani 1 , Sumie Koike 1 , Takuya Sakashita 1 , Satoru Kitazono 1 , Makoto Nishio 1 , Yasushi Okuno 2 , Jeffrey A. Engelman 3 , Alice T. Shaw 3 , Naoya Fujita 1 . 1 Japanese Foundation for Cancer Research, Tokyo, Japan; 2 Graduate School of Medicine, Kyoto University, Kyoto, Japan; 3 Massachusetts General Hospital Cancer Center, Boston, MA3591: Inhibition of heme oxygenase 1 decreases proliferation and resensitizes TKI-resistant Flt3-ITD-positive AML cellsTuesday, Apr 21, 2015, 8:00 AM -12:00 PMMary E. Irwin, Joya Chandra. UT MD Anderson Cancer Center, Houston, TX3592: Androgens interfere with enzalutamide agonism of mutant F876L androgen receptorTuesday, Apr 21, 2015, 8:00 AM -12:00 PMDaniel Coleman 1 , Katy Van Hook 1 , Robert Lisac 1 , Carly King 1 , Nicholas Wang 1 , Jacob Schwartzman 1 , Martin Gleave 2 , Lina Gao 1 , Joshua Urrutia 1 , Laura Heiser 1 , Joshi J. Alumkal 1 . 1 Oregon Health & Science University, Portland, OR; 2 University of British

Columbia, Vancouver, BC, Canada3593: Raptor upregulation contributes to maintenance of 4EBP1 phosphorylation and TORC kinase resistance in renal cancer cellsTuesday, Apr 21, 2015, 8:00 AM -12:00 PMPhilip Earwaker, Frances Willenbrock, Andrew Protheroe, Valentine Macaulay. University of Oxford, Oxford, United Kingdom3594: P-glycoprotein attenuates Src activation and DNA repair activity via increased C-terminal Src kinase-binding protein, a negative regulator of Src, in multidrug-resistant cellsTuesday, Apr 21, 2015, 8:00 AM -12:00 PMLi-Fang Lin, Ming-Hsi Wu, Tsann-Long Su, Te-Chang Lee. Academia Sinica - Inst. of Biomedical Sci., Taipei, Taiwan3595: In vivo acquired resistance to the mutant EGFR inhibitor Rociletinib (CO-1686) is associated with activation of the c-MET pathwayTuesday, Apr 21, 2015, 8:00 AM -12:00 PMHenry J. Haringsma, Andrew Allen, Thomas C. Harding, Andrew D. Simmons. Clovis Oncology, Inc., San Francisco, CA3596: A biomarker study of lapatinib in the neoadjuvant treatment of HER2 over expressing esophago-gastric adenocarcinoma (EGA)Tuesday, Apr 21, 2015, 8:00 AM -12:00 PMNadeera K. De Silva 1 , Laura Schulz 1 , Anna Paterson 1 , Tara Nuckcheddy-Grant 1 , Wendi Qain 1 , Edmund Godfrey 2 , Heok Cheow 2 , Maria O'Donovon 2 , Minesh Jobanputra 3 , Daniel Hochhauser 4 , Rebecca C. Fitzgerald 1 , Hugo Ford 2 . 1 University of Cambridge, Cambridge, United Kingdom; 2 Addenbrooke's Hospital, Cambridge, United Kingdom; 3 Galxosmithkline, Stevenage, United Kingdom; 4 University College London, London, United Kingdom3597: EZH2 D1 domain mutants confer acquired resistance to EZH2-targeted inhibitors and reprogram B-cell transcriptionTuesday, Apr 21, 2015, 8:00 AM -12:00 PMFrancois Gonzalvez, Theresa Baker, Justin Pritchard, Victor M. Rivera, Andrew Garner. ARIAD Pharmaceuticals, Inc., Cambridge, MA3598: Selective internal radiation (SIRT) is most effective when comparing local treatment to control progressive liver metastases of gastro-intestinal stromal tumors beyond treatment with tyrosine kinase inhibitorsTuesday, Apr 21, 2015, 8:00 AM -12:00 PMPeter Hohenberger 1 , Nils Rathmann 2 , Franka Menge 1 , Maliha Sadick 2 , Stefan Schönberg 2 , Steffen Diehl 2 . 1 Chirurgische Univ. Klinik, Mannheim, Germany; 2 Institut für Klinische Radiologie und Nuklearmedizin, Mannheim, Germany3599: Resistance mechanisms to HER2-targeting treatment in HER2-positive gastric cancerTuesday, Apr 21, 2015, 8:00 AM -12:00 PMKyo Hwa Kang 1 , Ah-Rong Nam 1 , Ji Eun Park 1 , Ju-Hee Bang 1 , Jin Ling 1 , Mei Hua Jin 1 , Tae Yong Kim 2 , Sae-Won Han 2 , Sang-Hyun Song 1 , Seock-Ah Im 2 , Tae-You Kim 2 , Do-Youn Oh 2 , Yung-Jue Bang 2 . 1 Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea, Republic of; 2 Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea; Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea, Republic of

3600: Impaired taxane binding to MTs in intrinsically taxane resistant gastric cancer cells without β-tubulin mutationTuesday, Apr 21, 2015, 8:00 AM -12:00 PMKatsuhiro Kita 1 , Giuseppe Galletti 1 , Kyle Cleveland 1 , Prashant V. Thakkar 1 , Ada Gjyrezi 1 , Chao Zhang 1 , Isabel Barasoain 2 , J. Fernando Díaz 2 , Doron Betel 1 , Manish A. Shah 1 , Paraskevi Giannakakou 1 . 1 Weill Medical College of Cornell University, New York, NY; 2 Centro de Investigaciones Biológicas, Consejo Superíor de Investigaciones Científicas (CIB-CSIC), Madrid, Spain3601: Antibody-drug conjugates (ADCs) with tubulysin and PBD warheads, maintain potent in vitro cytotoxicity against multidrug-resistant tumor cells expressing P-glycoprotein (P-gp)Tuesday, Apr 21, 2015, 8:00 AM -12:00 PMShenlan Mao 1 , Ryan Fleming 2 , Binyam Bezabeh 2 , Nazzareno Dimasi 2 , Dorin Toader 2 , Thais Cailleau 3 , Philip Howard 3 , Changshou Gao 2 , Bob Hollingsworth 1 , Adeela Kamal 1 , Jay Harper 1 . 1 Oncology Research, MEDIMMUNE, Gaithersburg, MD; 2 Antibody & Protein Engineering, MEDIMMUNE, Gaithersburg, MD; 3 Spirogen, MEDIMMUNE, Gaithersburg, MD3602: Cross-resistance to 1st, 2nd, and 3rd generation EGFR tyrosine kinase inhibitors in vitro is characterized by MET amplification and PTEN loss Tuesday, Apr 21, 2015, 8:00 AM -12:00 PMSarah M. Paul, Dorothee Nickles, Xioafen Ye, Robert L. Yauch, David S. Shames. Genentech, South San Francisco, CA3603: Molecular targeting of cetuximab resistant head and neck cancerTuesday, Apr 21, 2015, 8:00 AM -12:00 PMAdam D. Swick, Dana Gunderson, Molly Smith, Grace Blitzer, Andrew Stein, Kwangok P. Nickel, Randall J. Kimple. University of Wisconsin, Madison, WI3604: Targeting the PIM kinases in combination with BTK inhibition is synergistic in preclinical models of B-cell malignanciesTuesday, Apr 21, 2015, 8:00 AM -12:00 PMJeremiah J. Bearss, Brigham L. Bahr, Katie K. Soh, Peter W. Peterson, Clifford J. Whatcott, Adam Siddiqui-Jain, David J. Bearss, Steven L. Warner. Tolero Pharmaceuticals, Inc., Lehi, UT3605: Combined inhibition of IL-1, CXCR1/2, and TGFβ signaling pathways modulates in vivo acquired resistance to anti-VEGF treatmentTuesday, Apr 21, 2015, 8:00 AM -12:00 PMCarmine Carbone, Anna Tamburrino, Geny Piro, Marco Zanotto, Maria Mihaela Mina, Silvia Zanini, Federico Boschi, Aldo Scarpa, Giampaolo Tortora, Davide Melisi. University of Verona, Verona, Italy3606: Increase of MET gene copy number confers resistance to a monovalent MET antibody and establishes drug dependence.Tuesday, Apr 21, 2015, 8:00 AM -12:00 PMValentina Martin 1 , Simona Corso 2 , Paolo Maria Comoglio 3 , Silvia Giordano 4 . 1 University of Torino, Department of Oncology; Candiolo Cancer Institute, FPO-IRCCS, Candiolo (Torino), Italy; 2 University of Torino,Department of Oncology; Candiolo Cancer Institute, FPO-IRCCS;, Candiolo (Torino), Italy; 3 University of Torino, Department of Oncology;

Candiolo Cancer Institute, FPO-IRCCS;, Candiolo (Torino), Italy; 4 University of Torino, Department of Oncology, Candiolo Cancer Institute, FPO-IRCCS, Candiolo (Torino), Italy3607: Loss-of-function screens using haploid KBM7 and HAP1 cells to identify mechanisms of anti-cancer drug resistance.Tuesday, Apr 21, 2015, 8:00 AM -12:00 PMNora M. Gerhards 1 , Charlotte Guyader 2 , Vincent A. Blomen 2 , Aslı Küçükosmanoğlu 2 , Olaf van Tellingen 2 , Daniel J. Vis 2 , Lodewyk F. Wessels 2 , Thijn R. Brummelkamp 2 , Piet Borst 2 , Sven Rottenberg 1 . 1 Institute of Animal Pathology, Bern, Switzerland; 2 Netherlands Cancer Institute, Amsterdam, Netherlands

Session Title: Drug ResistanceSession Type: Plenary SessionSession Start/End Time: Tuesday, Apr 21, 2015, 8:15 AM -10:15 AMLocation: Hall A (200 Level), Pennsylvania Convention CenterCME: CME-DesignatedCME/CE Hours: 2Session Description: Drug resistance is the primary challenge faced by all practicing

oncologists. The advent of targeted therapies has provided exciting opportunities not only to understand the mechanisms through which resistance occurs, but also to design approaches that overcome this resistance. The presentations in this session will describe the latest developments in this area of research, from the perspectives of genetics, drug development, clinical application, and cell biology.

Presentations:ChairpersonTuesday, Apr 21, 2015, 8:15 AM -10:15 AMBert Vogelstein . Johns Hopkins Kimmel Comp. Cancer Center, Baltimore, MD Drug resistance: A genetic perspectiveTuesday, Apr 21, 2015, 8:15 AM - 8:45 AMBert Vogelstein . Johns Hopkins Kimmel Comp. Cancer Center, Baltimore, MD Genetic screens to understand drug resistanceTuesday, Apr 21, 2015, 8:45 AM - 9:15 AMAlan Ashworth . UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CADrug resistance: Translating discoveries into the clinicTuesday, Apr 21, 2015, 9:15 AM - 9:45 AMAlice T. Shaw . Massachusetts General Hospital Cancer Center, Boston, MA Drug resistance: A cell biologist's perspectiveTuesday, Apr 21, 2015, 9:45 AM -10:15 AMJoan S. Brugge . Harvard Medical School, Boston, MA

Session Title: Novel Mechanisms of Drug Response, Sensitivity, or Resistance 1Session Type: Poster SessionSession Start/End Time: Tuesday, Apr 21, 2015, 1:00 PM - 5:00 PM

Location: Section 29CME: (not eligible for CME credit)Session Category: Experimental and Molecular TherapeuticsPresentations:

4414: RhoA activation in diffuse type gastric adenocarcinoma promotes cancer stem cell phenotypes including chemotherapy resistanceTuesday, Apr 21, 2015, 1:00 PM - 5:00 PMChanghwan Yoon, Soo-Jeong Cho, Bulent A. Aksoy, Do Joong Park, Sam S. Yoon. Memorial Sloan Kettering Cancer Center, New York, NY4415: Tyrosine phosphorylation is essential for OCT2 function and a target of inhibition by TKIsTuesday, Apr 21, 2015, 1:00 PM - 5:00 PMNavjotsingh Pabla 1 , Jason A. Sprowl 2 , Su Sien Ong 3 , Alice A. Gibson 1 , Guoqing Du 1 , Wenwei Lin 3 , Shuiying Hu 1 , Lie Li 1 , Taosheng Chen 3 , Alex Sparreboom 1 . 1 Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN; 2 Department of Pharmaceutical, Social and Administrative Sciences, School of Pharmacy, D’Youville College, Buffalo, NY; 3 Department of Chemical Biology & Therapeutics, St. Jude Children's Research Hospital, Memphis, TN4416: Reversal of chemoresistance in ovarian cancer cells by the liposomal co-delivery of MDR inhibitors and paclitaxelTuesday, Apr 21, 2015, 1:00 PM - 5:00 PMShravan K. Sriraman 1 , Yilin Zhang 2 , Ed Luther 1 , Ernst Lengyel 2 , Vladimir Torchilin 1 , Vladimir Torchilin 3 . 1 Northeastern University, Boston, MA; 2 University of Chicago, Chicago, IL; 3 Faculty of Pharmacy, King Abdulaziz University, Saudi Arabia 4417: Vatalanib targets ABCG2-overexpressing multidrug resistant colon cancer cells under hypoxiaTuesday, Apr 21, 2015, 1:00 PM - 5:00 PMKenneth K. To 1 , Daniel C. Poon 1 , Yuming Wei 1 , Fang Wang 2 , Ge Lin 1 , Li-wu Fu 2 . 1 The Chinese University of Hong Kong, Hong Kong, Hong Kong; 2 Sun Yat-Sen University, Guangzhou, China4418: Autophagy induction contributes to cisplatin resistance in ovarian cancer and is independent of AKT pathway activityTuesday, Apr 21, 2015, 1:00 PM - 5:00 PMEmma L. Kipps 1 , Mike I. Walton 1 , Udai Banerji 1 , Stan B. Kaye 2 , Michelle D. Garrett 3 . 1 Institute of Cancer Research, London, United Kingdom; 2 The Drug Development Unit, Royal Marsden NHS Foundation Trust, London, United Kingdom; 3 School of Biosciences, University of Kent, Kent, United Kingdom4419: Design, synthesis and biological evaluation of N-aryl-3,3,3-trifluoro-2-hydroxy-2-methylpropionamide analog as a promising inhibitor of the multidrug resistance-linked ABCG2 transporterTuesday, Apr 21, 2015, 1:00 PM - 5:00 PMAtish S. Patel 1 , Tianwen Li 2 , Nagaraju Anreddy 3 , Yufen Zhao 2 , Rishil J. Kathawala 3 , Yijun Wang 3 , Suresh V. Ambudkar 1 , Zhe-Sheng Chen 3 , Changmei Cheng 2 . 1 National Cancer Institute, Bethesda, MD; 2 Tsinghua University, Bejing, China; 3 St. John's University,

Quenns, NY4420: Factors potentially contributing to sensitivities of CD22-targeting agents in B-cell malignanciesTuesday, Apr 21, 2015, 1:00 PM - 5:00 PMXin Yao, Patricia Burke, Joyce O. Obidi, Xiaoru Chen, Haifeng Bao, Yihong Yao, Jiaqi Huang. Medimmune LLC, Gaithersburg, MD4421: GPER-mediated activation of the cAMP response element-binding protein (CREB) and subsequent IGFBP-1 expression is altered during the development of tamoxifen resistanceTuesday, Apr 21, 2015, 1:00 PM - 5:00 PMAli Vaziri-Gohar 1 , Kevin D. Houston 2 . 1 New Mexico State University, Molecular Biology Program, Las Cruces, NM; 2 New Mexico State University, Molecular Biology Program and Chem. Biochem. Department, Las Cruces, NM4422: TTT-28, a newly synthesized thiazole-valine peptide, antagonizes multidrug resistance by inhibiting the efflux activity of the ABCB1 transporterTuesday, Apr 21, 2015, 1:00 PM - 5:00 PMYi-Jun Wang 1 , Nagaraju Anreddy 1 , Bhargav A. Patel 1 , Eduardo E. Chufan 2 , Satyakam Singh 1 , Guan-Nan Zhang 1 , Yun-Kai Zhang 1 , Anna Maria Barbuti 1 , Suresh V. Ambudkar 1 , Tanaji T. Talele 1 , Zhe-Sheng Chen 1 . 1 St. John's University, Queens, NY; 2 National Institutes of Health, Bethesda, MD4423: Chemoresistance regulation by COL11A1 in ovarian cancerTuesday, Apr 21, 2015, 1:00 PM - 5:00 PMYi-Hui Wu. National Cheng Kung University, Tainan, Taiwan4424: Molecular diagnostics of drug resistant multiple myeloma cases using targeted next generation sequencingTuesday, Apr 21, 2015, 1:00 PM - 5:00 PMHiroshi Ikeda, Yasushi Sasaki, Tetsuyuki Igarashi, Yuka Aoki, Toshiaki Hayashi, Tadao Ishida, Takashi Tokino, Yasuhisa Sinomura. Sapporo Medical University, Sapporo, Japan4425: Multiple -omic analyses of a pair of primary HCC tumor cell lines with different drug response revealed the mechanisms of drug resistanceTuesday, Apr 21, 2015, 1:00 PM - 5:00 PMGang Hu 1 , Alicia Du 1 , Yong Huang 1 , Kunyan Liu 1 , Fubo Xie 1 , Xuzhen Tang 1 , Xueyan Yang 1 , Qi Gu 1 , Yixin Zhang 2 , Weikang Tao 1 , Yingjia Zhang 1 , Wei Tang 1 , He Zhou 1 . 1 Shanghai ChemPartner Co., Ltd., Shanghai, China; 2 Nantong Cancer Hospital, Nantong, China4426: A 13 mer LNA miR-221 inhibitor restores drug sensitivity in melphalan-refractory multiple myeloma cellsTuesday, Apr 21, 2015, 1:00 PM - 5:00 PMAnnamaria Gulla 1 , Maria Teresa Di Martino 1 , Maria Eugenia Gallo Cantafio 1 , Eugenio Morelli 1 , Nicola Amodio 1 , Cirino Botta 1 , Maria Rita Pitari 1 , Santo Giovanni Lio 2 , Pierosandro Tagliaferri 1 , Pierfrancesco Tassone 1 . 1 Magna Graecia University, Catanzaro, Italy; 2 ‘‘Giovanni Paolo II’’ Hospital, Lamezia Terme, Italy 4427: Apoptosis, autophagy and ATP: The dynamic interaction of cellular ATP and drug resistance in MET amplified gastric cancerTuesday, Apr 21, 2015, 1:00 PM - 5:00 PM

Rebecca Dunbar Schroeder, David Hong, David J. McConkey. UT MD Anderson Cancer Center, Houston, TX4428: Metformin effects on ABCB1 expression and proliferation in pancreatic cancer cell lines with different ABCB1 genotypes/haplotypesTuesday, Apr 21, 2015, 1:00 PM - 5:00 PMBeverly D. Lyn-Cook 1 , Taylor Osborne 2 , Stancy Joseph 1 , Beverly Word 1 , Li Pang 1 , George Hammons 1 . 1 FDA-NCTR, Jefferson, AR; 2 University of Arkansas at Pine Bluff, Jefferson, AR4429: EGR1- MIR152 pathway overcomes acquired cisplatin resistance in ovarian cancer cells by inhibiting cyto-protective autophagy via ATG14Tuesday, Apr 21, 2015, 1:00 PM - 5:00 PMJun He 1 , Jing-Jie Yu 2 , Bing-Hua Jiang 1 . 1 Thomas Jefferson University, Philadelphia, PA; 2 West Virginia University, Morgantown, WV 4430: Loss of the histone methyltransferase EZH2 induces chemoresistance in acute myeloid leukemia (AML)Tuesday, Apr 21, 2015, 1:00 PM - 5:00 PMStefanie Göllner 1 , Shuchi Agrawal-Singh 2 , Tino Schenk 3 , Hans-Ulrich Klein 4 , Christian Rohde 1 , Tim Sauer 5 , Mads Lerdrup 2 , Sigal Tavor 6 , Friedrich Stölzel 7 , Gerhard Ehninger 7 , Gabriele Köhler 8 , Martin Dugas 5 , Arthur Zelent 9 , Christian Thiede 7 , Wolfgang E. Berdel 5 , Klaus Hansen 2 , Carsten Müller-Tidow 1 . 1 University Hospital of Halle (Saale), Halle (Saale), Germany; 2 Biotech Research and Innovation Centre and Centre for Epigenetics, University of Copenhagen, Copenhagen, Denmark; 3 Institute of Cancer Research (ICR), London, United Kingdom; 4 Brigham and Women's Hospital, Harvard Medical School, Boston, MA; 5 University Hospital of Münster, Münster, Germany; 6 Goldyne Savad Institute of Gene Therapy, Jerusalem, Israel; 7 University Hospital Carl Gustav Carus, Dresden, Germany; 8 Institute of Pathology, Klinikum Fulda, Fulda, Germany; 9 Sylvester Comprehensive Cancer Center (UMHC), University of Miami, Miami, FL4431: Musashi enhances GS3K-beta and promotes stemness-related chemoresistance in glioblastomaTuesday, Apr 21, 2015, 1:00 PM - 5:00 PMHsiao-Yun Chen, Shih-Hwa Chiou. National Yang Ming University, Taipei, Taiwan4432: A-803467, a tetrodotoxin-resistant sodium channel blocker, modulates ABCG2-mediated MDR in vitro and in vivoTuesday, Apr 21, 2015, 1:00 PM - 5:00 PMNagaraju Anreddy 1 , Atish Patel 1 , Yun-Kai Zhang 1 , Yi-Jun Wang 1 , Suneet Shukla 2 , Rishil J. Kathawala 1 , Priyank Kumar 1 , Pranav Gupta 1 , Suresh V. Ambudkar 2 , John ND Wurpel 1 , Zhe-Sheng Chen 1 . 1 St. John's University, Queens, NY; 2 National Institutes of Health, Bethesda, MD4433: P-gp-overexpressing MDR cells shed larger extracellular vesicles than their drug-sensitive counterpartsTuesday, Apr 21, 2015, 1:00 PM - 5:00 PMVanessa Lopes-Rodrigues 1 , Alessio Di Luca 2 , Diana Sousa 3 , Hugo Seca 4 , Paula Meleady 2 , Michael Henry 2 , Raquel T. Lima 5 , Robert O'Connor 2 , M. Helena Vasconcelos 3 . 1 Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP); Institute of Biomedical Sciences Abel Salazar, University of Porto (ICBAS-UP); Center of Medicinal

Chemistry of the University of Porto (CEQUIMED-UP), Porto, Portugal; 2 National Institute for Cellular Biotechnology (NICB), Dublin City University, Dublin, Ireland; 3 Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP); Department of Biological Sciences, Laboratory of Microbiology, Faculty of Pharmacy, University of Porto, Porto, Portugal; 4 Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal; 5 Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP); Center of Medicinal Chemistry of the University of Porto (CEQUIMED-UP), Porto, Portugal4434: Selinexor and melphalan combination therapy for the treatment of multiple myelomaTuesday, Apr 21, 2015, 1:00 PM - 5:00 PMJoel G. Turner 1 , Jana L. Dawson 1 , Christopher Cubitt 1 , Taiga Nishihori 1 , Claudio Anasetti 1 , Melissa Alsina 1 , Rachid C. Baz 1 , Michael Kauffman 2 , Sharon Shacham 2 , William S. Dalton 1 , Daniel M. Sullivan 1 . 1 Moffitt Cancer Center & Research Institute, Tampa, FL; 2 Karyopharm Therapeutics, Natick, MA 4436: Metformin upregulates hENT1 expression and enhances gemcitabine efficacy in pancreatic cancer cellsTuesday, Apr 21, 2015, 1:00 PM - 5:00 PMStancy J. Joseph, Taylor Osborne, Beverly Word, Beverly Lyn-Cook. NCTR/FDA, Jefferson, AR4437: The relevance of aberrant FPGS splicing for ex vivo MTX resistance and clinical outcome in childhood acute lymphoblastic leukemiaTuesday, Apr 21, 2015, 1:00 PM - 5:00 PMAnna Wojtuszkiewicz 1 , Yehuda G. Assaraf 2 , Mirthe Hoekstra 1 , Gerrit Jansen 1 , Godefridus J. Peters 1 , Edwin Sonneveld 3 , Gertjan L. Kaspers 1 , Jacqueline Cloos 1 . 1 VU Medical Center, Amsterdam, Netherlands; 2 Technion - Israel Institute of Technology, Haifa, Israel; 3 Dutch Childhood Oncology Group (DCOG), The Hague, Netherlands4439: Ero1L is a determinant of resistance to bortezomib and collateral sensitivity to MTI-101-induced cell death in myelomaTuesday, Apr 21, 2015, 1:00 PM - 5:00 PMMichael Emmons 1 , Lori Hazlehurst 1 , Steven Escherich 1 , Mark McLaughlin 1 , Javier Cuevas 2 , Daniel Sullivan 1 . 1 H. Lee Moffitt Cancer Ctr. & Res. Inst., Tampa, FL; 2 Univerity of South Florida, Tampa, FL4440: The functional role of insulin-like growth factor binding protein-2 in esophageal adenocarcinoma chemoresistanceTuesday, Apr 21, 2015, 1:00 PM - 5:00 PMAmy L. Myers, Lin Lin, Derek J. Nancarrow, Zhuwen Wang, Daysha Ferrer-Torres, David G. Beer, Andrew C. Chang. University of Michigan Medical Center, Ann Arbor, MI4442: TP53 hot spot mutations in ovarian cancer: Selective resistance to microtubule stabilizing agents in monoclonal cells and comparison of clinical outcomes from The Cancer Genome Atlas dataTuesday, Apr 21, 2015, 1:00 PM - 5:00 PMBrandon-Luke L. Seagle 1 , Gerda Hofstteter 2 , Chia-Ping Yang 2 , Kevin Eng 3 , Oluwatosin Odunsi-Akanji 1 , Kunle Odunsi 3 , Shohreh Shahabi 1 . 1 Western Connecticut Health Network, Danbury, CT; 2 Albert Einstein College of Medicine, Bronx, NY; 3 Roswell Park Cancer Institute, Buffalo, NY

4443: PB-42: Design and characterization of a glutathione pro-drug selectively delivered to normal tissue and not tumor tissueTuesday, Apr 21, 2015, 1:00 PM - 5:00 PMJames P. Thomas 1 , Peter G. Geiger 2 . 1 Medical College of Wisconsin, Milwaukee, WI; 2 Persictus Biosciences, Madison, WI

Session Title: AstraZeneca: Advanced Epidermal Growth Factor Receptor Mutation-positive Non-small Cell Lung Cancer: Understanding the Drivers of Resistance

Session Type: Exhibitor Spotlight PresentationSession Start/End Time: Tuesday, Apr 21, 2015, 3:00 PM - 4:00 PMLocation: Exhibitor Spotlight Theater A, Halls B-ESession Description: Lung cancer is the second most common cancer among both men and

women in the United States, and despite advances in treatment over the past several decades, mortality for lung cancer remains high. In a proportion of non-small cell lung cancer (NSCLC) patients, mutations in the Epidermal Growth Factor Receptor (EGFR) gene drive tumor growth and progression, and as a result EGFR has become an important therapeutic target for these tumors. This presentation aims to educate on the molecular biology of EGFR mutation-positive (EGFRm) NSCLC from diagnosis through disease progression and resistance, as well as educate on patient identification practices at diagnosis and progression.

Presentation:Advanced Epidermal Growth Factor Receptor Mutation-Positive Non-Small Cell Lung Cancer: Understanding the Drivers of ResistanceTuesday, Apr 21, 2015, 3:00 PM - 4:00 PMJeffrey Ross , Mark Socinski . AstraZeneca, Pittsburgh, PA

Session Title: Novel Mechanisms of Drug Response, Sensitivity, or Resistance 2Session Type: Poster SessionSession Start/End Time: Wednesday, Apr 22, 2015, 8:00 AM -12:00 PMLocation: Section 32CME: (not eligible for CME credit)Session Category: Experimental and Molecular TherapeuticsPresentations:

5449: Transfection of connexin 43 enhances sunitinib-induced apoptosis in malignant mesothelioma cells possibly via its interaction with BaxWednesday, Apr 22, 2015, 8:00 AM -12:00 PMMiaki Uzu, Hiromi Sato, Tatsuro Kashiba, Takuya Fujiwara, Yukihiro Shibata, Katsunori Yamaura, Akihiro Hisaka. Chiba University, Chiba, Japan5450: Naturally occurring mutations in the MPS1 gene predispose cells to kinase inhibitor

drug-resistanceWednesday, Apr 22, 2015, 8:00 AM -12:00 PMMark D. Gurden, Isaac Westwood, Amir Faisal, Sébastien Naud, Jack Cheung, Craig McAndrew, Amy Wood, Jessica Schmitt, Kathy Boxall, Grace Mak, Paul Workman, Rosemary Burke, Swen Hoelder, Julian Blagg, Rob Van Montfort, Spiros Linardopoulos. Institute of Cancer Research, London, United Kingdom5451: Over-expression of NPM-ALK drives resistance to TKIs in ALK+ ALCL but is toxic upon drug withdrawal, permitting prolonged tumour control through discontinuous dosingWednesday, Apr 22, 2015, 8:00 AM -12:00 PMSoumya Sundara Rajan, Amit Dipak Amin, Matthew Groysman, Praechompoo Pongtornpipat, Jonathan Schatz. University Of Arizona, Tucson, AZ5452: Inhibition of sodium-independent and sodium-dependent nucleobase transport activities by tyrosine kinase inhibitorsWednesday, Apr 22, 2015, 8:00 AM -12:00 PMVijaya L. Damaraju, Michelle Kuzma, Carol E. Cass, Michael B. Sawyer. Cross Cancer Inst., Edmonton, AB, Canada5453: Different mechanism of Oxaliplatin resistance in human colorectal cancer cell linesWednesday, Apr 22, 2015, 8:00 AM -12:00 PMTomoki Yamano, Shuji Kubo, Aya Yano, Naohiro Tomita. Hyogo College of Medicine, Nishinomiya, Japan5454: Wogonin overcomes cisplatin resistance of head and neck cancer by targeting antioxidant defense mechanismsWednesday, Apr 22, 2015, 8:00 AM -12:00 PMJi Won Kim, Eun Hye Kim, Jin Young Park, Minsu Kwon, Jong-Lyel Roh. Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea, Republic of5455: Surface accumulation of receptor tyrosine kinases upon treatment with tyrosine kinase inhibitors and resulting enhancement of activity upon treatment cessationWednesday, Apr 22, 2015, 8:00 AM -12:00 PMAnne-Mette Bjerregaard, Michael V. Grandal, Camilla Frohlich, Trine Lindsted, Christina Egebjerg, Ivan D. Horac, Michael Kragh, Mikkel W. Pedersen. Symphogen A/S, Ballerup, Denmark5456: FGF9 gene amplification can induce resistance to anti-EGFR therapy in colorectal cancerWednesday, Apr 22, 2015, 8:00 AM -12:00 PMTakuro Mizukami 1 , Yosuke Togashi 2 , Eri Banno 2 , Masato Terashima 2 , Marco A de velasco 2 , Kazuko Sakai 2 , Yoshihiko Fujita 2 , Shuta Tomida 2 , Takako Eguchi Nakajima 1 , Narikazu Boku 1 , Kazuto Nishio 2 . 1 St.Marianna university school of medicine, Kanagawa, Japan; 2 Kinki university faculty of medicine, Osaka, Japan 5457: MAD2γ, a new MAD2 isoform, is ubiquitously expressed in distinct cell lines, reduces mitotic arrest, and associates with resistance to cisplatin-based chemotherapy in testicular germ cell tumorsWednesday, Apr 22, 2015, 8:00 AM -12:00 PMAlejandro Lopez-Saavedra, Rodrigo Caceres, Fernando Luna, Irwin Hernandez, Luis Alonso Herrera. Inst. Nacional de Cancerología, Mexico, Mexico

5458: Elevated level of Fibrillarin induces chemoresistance by interfering p53 pathway in cancersWednesday, Apr 22, 2015, 8:00 AM -12:00 PMTeng Xu 1 , Suthakar Ganapathy 2 , Meijun Long 3 , Chul Ha 1 , Zhi-Min Yuan 2 , Hang Su 1 . 1 University of Texas Health Science Center at SA, san anotnio, TX; 2 Harvard School of Public Health, Boston, MA; 3 The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China5459: Overcoming resistance to HER2-targeting drugs using CDK8 inhibitorsWednesday, Apr 22, 2015, 8:00 AM -12:00 PMMartina McDermott 1 , Laura Ivers 2 , Norma O'Donovan 2 , John Crown 3 , Igor Roninson 1 , Eugenia V. Broude 1 . 1 University of South Carolina College of Pharmacy, Columbia, SC; 2 National Institute for Cellular Biotechnology, Dublin City University, Dublin, Ireland; 3 St. Vincent's University Hospital, Dublin, Ireland 5460: Prevention of peritonitis carcinomatosa after adjuvant chemotherapy by the inhibition of RNA polymerase in drug-tolerant subpopulationsWednesday, Apr 22, 2015, 8:00 AM -12:00 PMSatoshi S. Nishizuka, Kohei Kume, Kei Sato, Takeshi Iwaya, Go Wakabayashi. Iwate Medical University School of Medicine, Morioka, Japan5461: Triapine-mediated ABCB1 induction via PKC induces widespread therapy unresponsiveness but is not underlying acquired triapine resistanceWednesday, Apr 22, 2015, 8:00 AM -12:00 PMWalter Miklos 1 , Karla Pelivan 2 , Christian Kowol 2 , Rita Dornetshuber-Fleiss 2 , Melanie Spitzwieser 2 , Margit Cichna-Markl 2 , Gunda Köllensperger 2 , Bernhard Keppler 2 , Walter Berger 1 , Petra Heffeter 1 . 1 Medical University of Vienna, Vienna, Austria; 2 University of Vienna, Vienna, Austria5462: Extracellular ATP promotes cancer cell drug resistance to tyrosine kinase inhibitors by competing for the ATP-binding site of tyrosine kinaseWednesday, Apr 22, 2015, 8:00 AM -12:00 PMXuan Wang, Yanrong Qian, Yunsheng Li, Xiaozhuo Chen. Ohio University, Athens, OH5463: Role of the endothelin axis in astrocyte and endothelial cell mediated chemoprotection of cancer cellsWednesday, Apr 22, 2015, 8:00 AM -12:00 PMMark S. Kim, Hyun Jin Choi, Ho-Jeong Lee, Junqin He, Qiuyu We, Robert R. Langley, Sin-Jin Kim, Isaiah J. Fidler. UT MD Anderson Cancer Center, Houston, TX5464: Host variation in OATP1B1 is associated with treatment outcome in pediatric AMLWednesday, Apr 22, 2015, 8:00 AM -12:00 PMChristina D. Drenberg, Stanley Pounds, Lei Shi, Shelley Orwick, Lie Li, Shuiying Hu, Alice Gibson, Raul Ribeiro, Jeffrey Rubnitz, Alex Sparreboom, Sharyn D. Baker. St. Jude Children's Research Hospital, Memphis, TN5465: Systematic interrogation of druggable pathways in pancreatic adenocarcinomas using pooled gene-knockdown lentiviral librariesWednesday, Apr 22, 2015, 8:00 AM -12:00 PMEdgar Ferrer-Lorenzo, Daniel P. Nussbaum, Peter Winter, Kris Wood. Duke University, Durham, NC5466: Integrative TCGA analyses identify Basonuclin1 (BNC1) as a key mediator for

platinum resistanceWednesday, Apr 22, 2015, 8:00 AM -12:00 PMSherry Y. Wu, Justyna Filant, Michael McGuire, Rajesha Rupaimoole, Sunila Pradeep, Anna Unruh, Herbrich Shelley, Cristina Ivan, Ruder Dennis, Cristian Rodriguez-Aguayo, Vasudha Sehgal, Takahito Miyake, Archana Nagaraja, Kshipra Gharpure, Guillermo Armaiz, Rebecca Previs, Gabriel Lopez-Berestein, Prahlad Ram, Keith Baggerly, Anil Sood. University of Texas M.D. Anderson Cancer Center, Houston, TX5467: BRCA1 N-terminal-deficient proteins provide PARP inhibitor and platinum resistanceWednesday, Apr 22, 2015, 8:00 AM -12:00 PMYifan Wang 1 , Andrea Bernhardy 1 , Emmanuelle Nicolas 1 , Ryan Winters 1 , Kathy Cai 1 , Kelly Duncan 1 , James Duncan 1 , Maria Harrell 2 , Elizabeth Swisher 2 , Neil Johnson 1 . 1 Fox Chase Cancer Center, Philadelphia, PA; 2 University of Washington, Seattle, WA 5468: Tirapazamine as a strategy to prevent cell dissemination and overcome drug resistanceWednesday, Apr 22, 2015, 8:00 AM -12:00 PMBarbara Muz, Pilar de la Puente, Feda Azab, Micah Luderer, Abdel Kareem Azab. Washington University in St Louis, Saint Louis, MO5469: Dexamethasone interrupts paclitaxel-induced apoptosis in solid tumor cellsWednesday, Apr 22, 2015, 8:00 AM -12:00 PMMarianna Zavodovskaya, Carrie Brachmann, Jorge DiMartino, Daniel Pierce. Celgene, San Francisco, CA5470: Blocking wound-induced tumor repopulation between chemotherapy cycles as a novel approach to abrogate chemoresistanceWednesday, Apr 22, 2015, 8:00 AM -12:00 PMAntonina V. Kurtova, Jing Xiao, Qianxing Mo, Senthil Pazhanisamy, Ross Krasnow, Seth P. Lerner, Fengju Chen, Terrence Roh, Erica Lay, Philip L. Ho, Keith S. Chan. Baylor College of Medicine, Houston, TX5471: Identification of OAT1/OAT3 as contributors to cisplatin nephrotoxicityWednesday, Apr 22, 2015, 8:00 AM -12:00 PMShuiying Hu 1 , Navjotsingh Pabla 1 , Laura J. Janke 1 , Lie Li 1 , Aksana Vasilyeva 1 , Jason A. Sprowl 2 , Alex Sparreboom 1 . 1 St. Jude Children's Research Hospital, Memphis, TN; 2 D'Youville College, Buffalo, NY 5472: Selinexor, a selective inhibitor of nuclear export (SINE), acts through NF-κB deactivation and combines with proteasome inhibitors to synergistically induce tumor cell deathWednesday, Apr 22, 2015, 8:00 AM -12:00 PMYosef Landesman, Trinayan Kashyap, Marsha Crochiere, Boris Klebanov, Sharon Friedlander, William Senapedis, Robert Carlson, Michael Kauffman, Sharon Shacham. Karyopharm Therapeutics, Newton, MA5473: Human cancer cells acquire chemoresistance to gemcitabine mainly through loss-of-function mutations in the DCK geneWednesday, Apr 22, 2015, 8:00 AM -12:00 PMAkira Horii, Yuriko Saiki, Tomohiro Nakano, Chiharu Kudo, Makoto Sunamura. Tohoku Univ. School of Medicine, Sendai, Japan

5474: PD-L1 regulates cisplatin chemoresistance in head and neck squamous cell carcinomaWednesday, Apr 22, 2015, 8:00 AM -12:00 PMRandall S. Ruffner, Andrew Ramsey, Bert W. O'Malley, Jr., Daqing Li. University of Pennsylvania, Philadelphia, PA5475: Cancer exosome promotes cisplatin resistance In bladder cancer and inhibition of exosome sensitizes bladder cancer cells to cisplatin chemotherapyWednesday, Apr 22, 2015, 8:00 AM -12:00 PMChiahao Wu 1 , Chris Silvers 1 , Elizabeths Guancial 1 , Jong-Wei Hsu 2 , Edward Messing 1 , Yi- Fen Lee 1 . 1 University of Rochester, Rochester, NY; 2 Cornell University, Ithaca, NY 5476: A novel PARP inhibitor resistance mechanism mediated by the RNA-binding protein HuRWednesday, Apr 22, 2015, 8:00 AM -12:00 PMSaswati N. Chand 1 , Akshay R. Kamath 1 , Nicole Meisner-Kober 2 , Charles J. Yeo 1 , Jordan M. Winter 1 , Jonathan R. Brody 1 . 1 Thomas Jefferson University, Philadelphia, PA; 2 Novartis Institutes for Biomedical Research, Basel, Switzerland 5477: MERIT40 is an Akt substrate that promotes resolution of DNA damage induced by chemotherapyWednesday, Apr 22, 2015, 8:00 AM -12:00 PMKristin K. Brown, Laleh Montaser-Kouhsari, Andrew H. Beck, Alex Toker. Beth Israel Deaconess Medical Center, Boston, MA5478: Curcumin mediates reversion to oxaliplatin-acquired resistance in colorectal cancer cell lines through modulation of nuclear factor κB (NFκB) and cyclin-dependent kinase 5 (CDK5)Wednesday, Apr 22, 2015, 8:00 AM -12:00 PMVicenç Ruiz de Porras 1 , Sara Bystrup 1 , Anna Martinez-Cardus 2 , Alba Ginés 1 , Laura Layos 3 , José Luis Manzano 3 , Cristina Bugés 3 , Albert Abad 4 , Eva Martinez-Balibrea 1 . 1 Institut d'investigació en ciències de la salut Germans Trias i Pujol (IGTP), Badalona, Spain; 2 Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute, L'Hospitalet de LLobregat, Spain; 3 Catalan Institut of Oncology, Badalona, Spain; 4 Oncology Unit, Hospital CIMA Sanitas, Barcelona, Spain