Cistrome Cancer: A Web Resource for Integrative Gene Regulation Modeling in Cancer
Cancer results from a breakdown of normal gene expression control, so the study of gene regulation is critical to cancer research. To gain insight into the transcriptional and epigenetic factors regulating abnormal gene expression patterns in cancers, we developed the Cistrome Cancer web resource (http://cistrome.org/CistromeCancer/). We conducted the systematic integration and modeling of over 10,000 tumor molecular profiles from The Cancer Genome Atlas (TCGA) with over 23,000 ChIP-seq and chromatin accessibility profiles from our Cistrome collection. The results include reconstruction of functional enhancer profiles, “...
Source: Cancer Research - October 31, 2017 Category: Cancer & Oncology Authors: Shenglin Mei, Clifford A. Meyer, Rongbin Zheng, Qian Qin, Qiu Wu, Peng Jiang, Bo Li, Xiaohui Shi, Binbin Wang, Jingyu Fan, Celina Shih, Myles Brown, Chongzhi Zang, X. Shirley Liu Tags: Focus on Computer Resources Source Type: research

Developing Cancer Informatics Applications and Tools Using the NCI Genomic Data Commons API
We describe the GDC API and how it has been used both by the GDC itself and by third parties. Cancer Res; 77(21); e15–18. ©2017 AACR. (Source: Cancer Research)
Source: Cancer Research - October 31, 2017 Category: Cancer & Oncology Authors: Shane Wilson, Michael Fitzsimons, Martin Ferguson, Allison Heath, Mark Jensen, Josh Miller, Mark W. Murphy, James Porter, Himanso Sahni, Louis Staudt, Yajing Tang, Zhining Wang, Christine Yu, Junjun Zhang, Vincent Ferretti, Robert L. Grossman Tags: Focus on Computer Resources Source Type: research

WebMeV: A Cloud Platform for Analyzing and Visualizing Cancer Genomic Data
Although large, complex genomic datasets are increasingly easy to generate, and the number of publicly available datasets in cancer and other diseases is rapidly growing, the lack of intuitive, easy-to-use analysis tools has remained a barrier to the effective use of such data. WebMeV (http://mev.tm4.org) is an open-source, web-based tool that gives users access to sophisticated tools for analysis of RNA-Seq and other data in an interface designed to democratize data access. WebMeV combines cloud-based technologies with a simple user interface to allow users to access large public datasets, such as that from The Cancer Gen...
Source: Cancer Research - October 31, 2017 Category: Cancer & Oncology Authors: Yaoyu E. Wang, Lev Kutnetsov, Antony Partensky, Jalil Farid, John Quackenbush Tags: Focus on Computer Resources Source Type: research

The ISB Cancer Genomics Cloud: A Flexible Cloud-Based Platform for Cancer Genomics Research
The ISB Cancer Genomics Cloud (ISB-CGC) is one of three pilot projects funded by the National Cancer Institute to explore new approaches to computing on large cancer datasets in a cloud environment. With a focus on Data as a Service, the ISB-CGC offers multiple avenues for accessing and analyzing The Cancer Genome Atlas, TARGET, and other important references such as GENCODE and COSMIC using the Google Cloud Platform. The open approach allows researchers to choose approaches best suited to the task at hand: from analyzing terabytes of data using complex workflows to developing new analysis methods in common languages such ...
Source: Cancer Research - October 31, 2017 Category: Cancer & Oncology Authors: Sheila M. Reynolds, Michael Miller, Phyliss Lee, Kalle Leinonen, Suzanne M. Paquette, Zack Rodebaugh, Abigail Hahn, David L. Gibbs, Joseph Slagel, William J. Longabaugh, Varsha Dhankani, Madelyn Reyes, Todd Pihl, Mark Backus, Matthew Bookman, Nicole Defla Tags: Focus on Computer Resources Source Type: research

The Cancer Genomics Cloud: Collaborative, Reproducible, and Democratized—A New Paradigm in Large-Scale Computational Research
The Seven Bridges Cancer Genomics Cloud (CGC; www.cancergenomicscloud.org) enables researchers to rapidly access and collaborate on massive public cancer genomic datasets, including The Cancer Genome Atlas. It provides secure on-demand access to data, analysis tools, and computing resources. Researchers from diverse backgrounds can easily visualize, query, and explore cancer genomic datasets visually or programmatically. Data of interest can be immediately analyzed in the cloud using more than 200 preinstalled, curated bioinformatics tools and workflows. Researchers can also extend the functionality of the platform by addi...
Source: Cancer Research - October 31, 2017 Category: Cancer & Oncology Authors: Jessica W. Lau, Erik Lehnert, Anurag Sethi, Raunaq Malhotra, Gaurav Kaushik, Zeynep Onder, Nick Groves-Kirkby, Aleksandar Mihajlovic, Jack DiGiovanna, Mladen Srdic, Dragan Bajcic, Jelena Radenkovic, Vladimir Mladenovic, Damir Krstanovic, Vladan Arsenijevi Tags: Focus on Computer Resources Source Type: research

Cancer Informatics: New Tools for a Data-Driven Age in Cancer Research
(Source: Cancer Research)
Source: Cancer Research - October 31, 2017 Category: Cancer & Oncology Authors: Warren Kibbe, Juli Klemm, John Quackenbush Tags: Focus on Computer Resources Source Type: research

Phenotypic Heterogeneity of Circulating Tumor Cells Informs Clinical Decisions between AR Signaling Inhibitors and Taxanes in Metastatic Prostate Cancer
The heterogeneity of an individual patient's tumor has been linked to treatment resistance, but quantitative biomarkers to rapidly and reproducibly evaluate heterogeneity in a clinical setting are currently lacking. Using established tools available in a College of American Pathologists–accredited and Clinical Laboratory Improvement Amendments–certified clinical laboratory, we quantified digital pathology features on 9,225 individual circulating tumor cells (CTC) from 179 unique metastatic castration-resistant prostate cancer (mCRPC) patients to define phenotypically distinct cell types. Heterogeneity was quantified on...
Source: Cancer Research - October 15, 2017 Category: Cancer & Oncology Authors: Howard I. Scher, Ryon P. Graf, Nicole A. Schreiber, Brigit McLaughlin, Adam Jendrisak, Yipeng Wang, Jerry Lee, Stephanie Greene, Rachel Krupa, David Lu, Pascal Bamford, Jessica E. Louw, Lyndsey Dugan, Hebert A. Vargas, Martin Fleisher, Mark Landers, Glenn Tags: Clinical Studies Source Type: research

T Cells Deficient in Diacylglycerol Kinase {zeta} Are Resistant to PD-1 Inhibition and Help Create Persistent Host Immunity to Leukemia
In this study, we evaluated the antileukemia activity of adoptively transferred polyclonal cancer antigen-reactive T cells deficient in the regulator diacylglycerol kinase zeta (DGKζ) with or without PD-1/PD-L1 blockade. In the C1498 mouse model of myeloid leukemia, we showed that leukemia was eradicated more effectively in DGKζ-deficient (DGKζ−/−) mice than wild-type mice. T cells transferred from DGKζ-deficient mice to wild-type tumor-bearing recipients conferred this benefit. Leukemia clearance was similar to mice treated with anti-PD-L1. Strikingly, we found that the activity of adoptively transferred DGKζ−/...
Source: Cancer Research - October 15, 2017 Category: Cancer & Oncology Authors: Weiqing Jing, Jill A. Gershan, Sandra Holzhauer, James Weber, Katie Palen, Laura McOlash, Kirthi Pulakanti, Erin Wesley, Sridhar Rao, Bryon D. Johnson, Matthew J. Riese Tags: Microenvironment and Immunology Source Type: research

GSK3 Inhibition Drives Maturation of NK Cells and Enhances Their Antitumor Activity
In this study, we show that pharmacologic inhibition of GSK3 kinase in peripheral blood NK cells expanded ex vivo with IL15 greatly enhances CD57 upregulation and late-stage maturation. GSK3 inhibition elevated the expression of several transcription factors associated with late-stage NK-cell maturation including T-BET, ZEB2, and BLIMP-1 without affecting viability or proliferation. When exposed to human cancer cells, NK cell expanded ex vivo in the presence of a GSK3 inhibitor exhibited significantly higher production of TNF and IFNγ, elevated natural cytotoxicity, and increased antibody-dependent cellular cytotoxicity. ...
Source: Cancer Research - October 15, 2017 Category: Cancer & Oncology Authors: Frank Cichocki, Bahram Valamehr, Ryan Bjordahl, Bin Zhang, Betsy Rezner, Paul Rogers, Svetlana Gaidarova, Stacey Moreno, Katie Tuininga, Phillip Dougherty, Valarie McCullar, Peter Howard, Dhifaf Sarhan, Emily Taras, Heinrich Schlums, Stewart Abbot, Daniel Tags: Microenvironment and Immunology Source Type: research

CD73 Promotes Resistance to HER2/ErbB2 Antibody Therapy
In conclusion, our findings establish CD73 in mediating resistance to trastuzumab and provide new insights into how CD73 is regulated in breast cancer. Cancer Res; 77(20); 5652–63. ©2017 AACR. (Source: Cancer Research)
Source: Cancer Research - October 15, 2017 Category: Cancer & Oncology Authors: Martin Turcotte, David Allard, Deepak Mittal, Yacine Bareche, Laurence Buisseret, Vinu Jose, Sandra Pommey, Vincent Delisle, Sherene Loi, Heikki Joensuu, Pirkko–Liisa Kellokumpu–Lehtinen, Christos Sotiriou, Mark J. Smyth, John Stagg Tags: Microenvironment and Immunology Source Type: research

{beta}-Adrenergic Signaling in Mice Housed at Standard Temperatures Suppresses an Effector Phenotype in CD8+ T Cells and Undermines Checkpoint Inhibitor Therapy
We report here that CD8+ T-cell frequency and functional orientation within the tumor microenvironment is regulated by β2-adrenergic receptor (β-AR) signaling in host immune cells. We used three strategies—physiologic (manipulation of ambient thermal environment), pharmacologic (β-blockers), and genetic (β2-AR knockout mice) to reduce adrenergic stress signaling in two widely studied preclinical mouse tumor models. Reducing β-AR signaling facilitated conversion of tumors to an immunologically active tumor microenvironment with increased intratumoral frequency of CD8+ T cells with an effector phenotype and decreased ...
Source: Cancer Research - October 15, 2017 Category: Cancer & Oncology Authors: Mark J. Bucsek, Guanxi Qiao, Cameron R. MacDonald, Thejaswini Giridharan, Lauren Evans, Brian Niedzwecki, Haichao Liu, Kathleen M. Kokolus, Jason W.-L. Eng, Michelle N. Messmer, Kristopher Attwood, Scott I. Abrams, Bonnie L. Hylander, Elizabeth A. Repasky Tags: Microenvironment and Immunology Source Type: research

Anti-Jagged Immunotherapy Inhibits MDSCs and Overcomes Tumor-Induced Tolerance
In this study, we assessed the therapeutic effect of the humanized anti–Jagged1/2-blocking antibody CTX014 on MDSC-mediated T-cell suppression in tumor-bearing mice. CTX014 decreased tumor growth, affected the accumulation and tolerogenic activity of MDSCs in tumors, and inhibited the expression of immunosuppressive factors arginase I and iNOS. Consequently, anti-Jagged therapy overcame tumor-induced T-cell tolerance, increased the infiltration of reactive CD8+ T cells into tumors, and enhanced the efficacy of T-cell–based immunotherapy. Depletion of MDSC-like cells restored tumor growth in mice treated with anti-Jagge...
Source: Cancer Research - October 15, 2017 Category: Cancer & Oncology Authors: Rosa A. Sierra, Jimena Trillo-Tinoco, Eslam Mohamed, Lolie Yu, Bhagelu R. Achyut, Ali Arbab, Jennifer W. Bradford, Barbara A. Osborne, Lucio Miele, Paulo C. Rodriguez Tags: Microenvironment and Immunology Source Type: research

Therapeutic Effects of XPO1 Inhibition in Thymic Epithelial Tumors
Exportin 1 (XPO1) mediates nuclear export of many cellular factors known to play critical roles in malignant processes, and selinexor (KPT-330) is the first XPO1-selective inhibitor of nuclear export compound in advanced clinical development phase for cancer treatment. We demonstrated here that inhibition of XPO1 drives nuclear accumulation of important cargo tumor suppressor proteins, including transcription factor FOXO3a and p53 in thymic epithelial tumor (TET) cells, and induces p53-dependent and -independent antitumor activity in vitro. Selinexor suppressed the growth of TET xenograft tumors in athymic nude mice via in...
Source: Cancer Research - October 15, 2017 Category: Cancer & Oncology Authors: Fabio Conforti, Xu Zhang, Guanhua Rao, Tommaso De Pas, Yoko Yonemori, Jose Antonio Rodriguez, Justine N. McCutcheon, Raneen Rahhal, Anna T. Alberobello, Yisong Wang, Yu-Wen Zhang, Udayan Guha, Giuseppe Giaccone Tags: Therapeutics, Targets, and Chemical Biology Source Type: research

Structurally Novel Antiestrogens Elicit Differential Responses from Constitutively Active Mutant Estrogen Receptors in Breast Cancer Cells and Tumors
Many estrogen receptor α (ERα)–positive breast cancers develop resistance to endocrine therapy via mutation of ERs whose constitutive activation is associated with shorter patient survival. Because there is now a clinical need for new antiestrogens (AE) against these mutant ERs, we describe here our development and characterization of three chemically novel AEs that effectively suppress proliferation of breast cancer cells and tumors. Our AEs are effective against wild-type and Y537S and D538G ERs, the two most commonly occurring constitutively active ERs. The three new AEs suppressed proliferation and estrogen target ...
Source: Cancer Research - October 15, 2017 Category: Cancer & Oncology Authors: Yuechao Zhao, Mary J. Laws, Valeria Sanabria Guillen, Yvonne Ziegler, Jian Min, Abhishek Sharma, Sung Hoon Kim, David Chu, Ben Ho Park, Steffi Oesterreich, Chengjian Mao, David J. Shapiro, Kendall W. Nettles, John A. Katzenellenbogen, Benita S. Katzenelle Tags: Therapeutics, Targets, and Chemical Biology Source Type: research

Monocarboxylate Transporter MCT1 Promotes Tumor Metastasis Independently of Its Activity as a Lactate Transporter
In this study, we present evidence of a function for MCT1 in metastasis beyond its role as a transporter of lactic acid. MCT1 activates transcription factor NF-κB to promote cancer cell migration independently of MCT1 transporter activity. Although pharmacologic MCT1 inhibition did not modulate MCT1-dependent cancer cell migration, silencing or genetic deletion of MCT1 in vivo inhibited migration, invasion, and spontaneous metastasis. Our findings raise the possibility that pharmacologic inhibitors of MCT1-mediated lactic acid transport may not effectively prevent metastatic dissemination of cancer cells. Cancer Res; 77(2...
Source: Cancer Research - October 15, 2017 Category: Cancer & Oncology Authors: Valery L. Payen, Myriam Y. Hsu, Kristin S. Radecke, Elisabeth Wyart, Thibaut Vazeille, Caroline Bouzin, Paolo E. Porporato, Pierre Sonveaux Tags: Therapeutics, Targets, and Chemical Biology Source Type: research