Rescue Screens with Secreted Proteins Reveal Compensatory Potential of Receptor Tyrosine Kinases in Driving Cancer GrowthCancer 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 LymphomaCancer 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 InhibitorCancer 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 InhibitorsCancer 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 ImmunotherapyCancer 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
Primary Resistance to PD-1 Blockade Mediated by JAK1/2 MutationsCancer 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 CancerCancer 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 ConsortiumCancer 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
Essential Gene Profiles in Breast, Pancreatic, and Ovarian Cancer CellsCancer Discovery - Tập 2 Số 2 - Trang 172-189 - 2012
Richard Marcotte, Kevin R. Brown, Fernando Suárez, Azin Sayad, Konstantina Karamboulas, Paul M. Krzyzanowski, Fabrice Sircoulomb, Mauricio Medrano, Yaroslav Fedyshyn, Judice L.Y. Koh, Dewald van Dyk, Fedyshyn Bohdana, Marianna Luhova, Glauber C. Brito, Franco J. Vizeacoumar, Frederick S. Vizeacoumar, Alessandro Datti, Dahlia Kasimer, Alla Buzina, Patricia Mero, Christine Misquitta, Josée Normand, Maliha Haider, Troy Ketela, Jeffrey L. Wrana, Robert Rottapel, Benjamin G. Neel, Jason Moffat
AbstractGenomic analyses are yielding a host of new information on the multiple genetic abnormalities associated with specific types of cancer. A comprehensive description of cancer-associated genetic abnormalities can improve our ability to classify tumors into clinically relevant subgroups and, on occasion, identify mutant genes that drive the cancer phenotype (“...... hiện toàn bộ
TYK2–STAT1–BCL2 Pathway Dependence in T-cell Acute Lymphoblastic LeukemiaCancer Discovery - Tập 3 Số 5 - Trang 564-577 - 2013
Takaomi Sanda, Jeffrey W. Tyner, Alejandro Gutiérrez, Vu N. Ngo, Jason Glover, Bill H. Chang, Arla Yost, Wenxue Ma, Angela G. Fleischman, Wenjun Zhou, Yandan Yang, Maria Kleppe, Yebin Ahn, Jessica Tatarek, Michelle A. Kelliher, Donna Neuberg, Ross L. Levine, Richard Moriggl, Mathias Müller, Nathanael S. Gray, Catriona Jamieson, Andrew P. Weng, Louis M. Staudt, Brian J. Druker, A. Thomas Look
Abstract
Targeted molecular therapy has yielded remarkable outcomes in certain cancers, but specific therapeutic targets remain elusive for many others. As a result of two independent RNA interference (RNAi) screens, we identified pathway dependence on a member of the Janus-activated kinase (JAK) tyrosine kinase family, TYK2, and its downstream effec...... hiện toàn bộ