Cancer Discovery

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Rescue Screens with Secreted Proteins Reveal Compensatory Potential of Receptor Tyrosine Kinases in Driving Cancer Growth
Cancer Discovery - Tập 2 Số 10 - Trang 948-959 - 2012
Fred Harbinski, Vanessa J. Craig, Sneha Sanghavi, Douglas A. Jeffery, Lijuan Liu, Kelly-Ann Sheppard, Sabrina Wagner, Christelle Stamm, Andreas Buneß, Christian Chatenay‐Rivauday, Yao Yao, Feng He, Chris X. Lu, Vito Guagnano, Thomas Metz, Peter M. Finan, Francesco Hofmann, William R. Sellers, Jeffrey A. Porter, Vic E. Myer, Diana Graus-Porta, Christopher J. Wilson, Alan Buckler, Ralph Tiedt
Abstract The overall power of kinase inhibitors is substantially overshadowed by the acquisition of drug resistance. To address this issue, we systematically assessed the potential of secreted proteins to induce resistance to kinase inhibitors. To this end, we developed a high-throughput platform for screening a cDNA library encoding 3,432 secreted p...... hiện toàn bộ
In Situ Vaccination with a TLR9 Agonist and Local Low-Dose Radiation Induces Systemic Responses in Untreated Indolent Lymphoma
Cancer Discovery - Tập 8 Số 10 - Trang 1258-1269 - 2018
Matthew J. Frank, Patrick M. Reagan, Nancy L. Bartlett, Leo I. Gordon, Jonathan W. Friedberg, Debra K. Czerwinski, Steven Long, Richard T. Hoppe, Robert Janssen, Albert F. Candia, Robert L. Coffman, Ronald Levy
Abstract This multicenter phase I/II clinical trial evaluated intratumoral SD-101, a TLR9 agonist, and low-dose radiation in patients with untreated indolent lymphoma. Twenty-nine enrolled patients received 4 Gy of radiation followed by 5 weekly intratumoral injections of SD-101 at a single tumor site. No treatment-related grade 4 or serious adverse ...... hiện toàn bộ
A High-Throughput Fluorimetric Assay for 2-Hydroxyglutarate Identifies Zaprinast as a Glutaminase Inhibitor
Cancer Discovery - Tập 4 Số 7 - Trang 828-839 - 2014
Adnan Elhammali, Joseph E. Ippolito, Lynne Collins, Jan R. Crowley, Jayne Marasa, David Piwnica‐Worms
Abstract Recently identified isocitrate dehydrogenase (IDH) mutations lead to the production of 2-hydroxyglutarate (2HG), an oncometabolite aberrantly elevated in selected cancers. We developed a facile and inexpensive fluorimetric microplate assay for the quantitation of 2HG and performed an unbiased small-molecule screen in live cells to identify c...... hiện toàn bộ
Activation of MET via Diverse Exon 14 Splicing Alterations Occurs in Multiple Tumor Types and Confers Clinical Sensitivity to MET Inhibitors
Cancer Discovery - Tập 5 Số 8 - Trang 850-859 - 2015
Garrett M. Frampton, Siraj M. Ali, Mark R. Rosenzweig, Juliann Chmielecki, Xinyuan Lu, Todd M. Bauer, Mikhail Akimov, José A. Bufill, Carrie B. Lee, David Jentz, Rick Hoover, Sai‐Hong Ignatius Ou, Ravi Salgia, Timothy J. Brennan, Zachary R. Chalmers, Savina Jaeger, Alan Huang, Julia A. Elvin, Rachel Erlich, Alex Fichtenholtz, Kyle Gowen, Joel Greenbowe, Adrienne Johnson, Depinder Khaira, Caitlin McMahon, Eric M. Sanford, Steven Roels, Jared White, Joel Greshock, Robert Schlegel, Doron Lipson, Roman Yelensky, Deborah Morosini, Jeffrey S. Ross, Eric A. Collisson, Malte Peters, Philip J. Stephens, Vincent A. Miller
Abstract Focal amplification and activating point mutation of the MET gene are well-characterized oncogenic drivers that confer susceptibility to targeted MET inhibitors. Recurrent somatic splice site alterations at MET exon 14 (METex14) that result in exon skipping and MET activation have been characterized, but their full diversity and prevalence a...... hiện toàn bộ
The HIF-1α Hypoxia Response in Tumor-Infiltrating T Lymphocytes Induces Functional CD137 (4-1BB) for Immunotherapy
Cancer Discovery - Tập 2 Số 7 - Trang 608-623 - 2012
Asís Palazón, Iván Martínez‐Forero, Álvaro Teijeira, Aizea Morales‐Kastresana, Carlos Alfaro, Miguel F. Sanmamed, José Luis Pérez‐Gracia, Iván Peñuelas, Sandra Hervás‐Stubbs, Ana Rouzaut, M O de Landázuri, Anna Maria Di Giacomo, Julián Aragonés, Ignacio Melero
AbstractThe tumor microenvironment of transplanted and spontaneous mouse tumors is profoundly deprived of oxygenation as confirmed by positron emission tomographic (PET) imaging. CD8 and CD4 tumor-infiltrating T lymphocytes (TIL) of transplanted colon carcinomas, melanomas, and spontaneous breast adenocarcinomas are CD137 (4-1BB)-positive, as opposed to their count...... hiện toàn bộ
Crebbp Loss Drives Small Cell Lung Cancer and Increases Sensitivity to HDAC Inhibition
Cancer Discovery - Tập 8 Số 11 - Trang 1422-1437 - 2018
Deshui Jia, Arnaud Augert, Dong Wook Kim, Emily Eastwood, Nan Wu, Ali H. Ibrahim, Kee‐Beom Kim, Colin T. Dunn, Smitha P.S. Pillai, Adi F. Gazdar, Hamid Bolouri, Kwon-Sik Park, David MacPherson
Abstract CREBBP, encoding an acetyltransferase, is among the most frequently mutated genes in small cell lung cancer (SCLC), a deadly neuroendocrine tumor type. We report acceleration of SCLC upon Crebbp inactivation in an autochthonous mouse model. Extending these observations beyond the lung, broad Crebbp deletion in mouse neuroendocrine cells coop...... hiện toàn bộ
Primary Resistance to PD-1 Blockade Mediated by JAK1/2 Mutations
Cancer Discovery - Tập 7 Số 2 - Trang 188-201 - 2017
Daniel Sanghoon Shin, Jesse M. Zaretsky, Helena Escuin-Ordinas, Ángel García-Díaz, Siwen Hu‐Lieskovan, Anusha Kalbasi, Catherine S. Grasso, Willy Hugo, Salemiz Sandoval, Davis Y. Torrejon, Nicolaos Palaskas, Gabriel Abril Rodriguez, Giulia Parisi, Ariel M. Azhdam, Bartosz Chmielowski, Grace Cherry, Elizabeth Seja, Beata Berent-Maoz, I. Peter Shintaku, Dung T. Le, Drew M. Pardoll, Luis A. Díaz, Paul C. Tumeh, Thomas G. Graeber, Roger S. Lo, Begoña Comı́n-Anduix, Antoni Ribas
Abstract Loss-of-function mutations in JAK1/2 can lead to acquired resistance to anti-programmed death protein 1 (PD-1) therapy. We reasoned that they may also be involved in primary resistance to anti–PD-1 therapy. JAK1/2-inactivating mutations were noted in tumor biopsies of 1 of 23 patients with melanoma and in 1 of 16 patients with mismatch repai...... hiện toàn bộ
Accelerating Discovery of Functional Mutant Alleles in Cancer
Cancer Discovery - Tập 8 Số 2 - Trang 174-183 - 2018
Matthew T. Chang, Tripti Shrestha Bhattarai, Alison M. Schram, Craig M. Bielski, Mark T.A. Donoghue, Philip Jonsson, Debyani Chakravarty, Sarah Phillips, Cyriac Kandoth, Alexander Penson, Alexander N. Gorelick, Tambudzai Shamu, Swati Patel, Christopher Harris, Jianjiong Gao, S. Onur Sumer, Ritika Kundra, Pedram Razavi, Bob T. Li, Dalicia N. Reales, Nicholas D. Socci, Gowtham Jayakumaran, Ahmet Zehir, Ryma Benayed, Maria E. Arcila, Sarat Chandarlapaty, Marc Ladanyi, Nikolaus Schultz, José Baselga, Michael F. Berger, Neal Rosen, David B. Solit, David M. Hyman, Barry S. Taylor
AbstractMost mutations in cancer are rare, which complicates the identification of therapeutically significant mutations and thus limits the clinical impact of genomic profiling in patients with cancer. Here, we analyzed 24,592 cancers including 10,336 prospectively sequenced patients with advanced disease to identify mutant residues arising more frequently than ex...... hiện toàn bộ
AACR Project GENIE: Powering Precision Medicine through an International Consortium
Cancer Discovery - Tập 7 Số 8 - Trang 818-831 - 2017
Fabrice André, Mónica Arnedos, Alexander S. Baras, José Baselga, Philippe L. Bédard, Michael F. Berger, Mariska Bierkens, Fabien Calvo, Ethan Cerami, Debyani Chakravarty, Kristen K. Dang, Nancy E. Davidson, Catherine Del Vecchio Fitz, Semih Doğan, Raymond N. DuBois, Matthew D. Ducar, P. Andrew Futreal, Jianjiong Gao, Francisco Moacir Pinheiro Garcia, Stuart M. Gardos, Christopher D. Gocke, Benjamin Groß, Justin Guinney, Zachary Heins, Stephanie Hintzen, Hugo M. Horlings, Jan Hudeček, David M. Hyman, Suzanne Kamel‐Reid, Cyriac Kandoth, Walter Kinyua, Priti Kumari, Ritika Kundra, Marc Ladanyi, Céline Lefèbvre, Michele L. Lenoue-Newton, Eva M. Lepisto, Mia A. Levy, Neal I. Lindeman, James Lindsay, David Liu, Zhibin Lu, Laura E. MacConaill, Ian Maurer, David S. Maxwell, Gerrit A. Meijer, Funda Meric‐Bernstam, Christine Micheel, Clinton Miller, Gordon B. Mills, Nathanael D. Moore, Petra M. Nederlof, Larsson Omberg, John A. Orechia, Ben Ho Park, Trevor J. Pugh, Brendan Reardon, Barrett J. Rollins, Mark J. Routbort, Charles L. Sawyers, Deborah Schrag, Nikolaus Schultz, Kenna Shaw, Priyanka Shivdasani, Lillian L. Siu, David B. Solit, Gabe S. Sonke, Jean‐Charles Soria, Parin Sripakdeevong, Natalie Stickle, Thomas Stricker, Shawn M. Sweeney, Barry S. Taylor, Jelle J. ten Hoeve, Stacy B. Thomas, Eliezer M. Van Allen, Laura J. van‘t Veer, Tony van de Velde, Harm van Tinteren, Victor E. Velculescu, Carl Virtanen, Emile E. Voest, Lucy Lu Wang, Chetna Wathoo, Stuart Watt, Celeste Yu, Thomas Yu, Emily Yu, Ahmet Zehir, Hongxin Zhang
Abstract The AACR Project GENIE is an international data-sharing consortium focused on generating an evidence base for precision cancer medicine by integrating clinical-grade cancer genomic data with clinical outcome data for tens of thousands of cancer patients treated at multiple institutions worldwide. In conjunction with the first public data rel...... hiện toàn bộ
Fundamental Mechanisms of Immune Checkpoint Blockade Therapy
Cancer Discovery - Tập 8 Số 9 - Trang 1069-1086 - 2018
Spencer C. Wei, Colm R. Duffy, James P. Allison
AbstractImmune checkpoint blockade is able to induce durable responses across multiple types of cancer, which has enabled the oncology community to begin to envision potentially curative therapeutic approaches. However, the remarkable responses to immunotherapies are currently limited to a minority of patients and indications, highlighting the need for more effecti...... hiện toàn bộ
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