Cancer Discovery

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Akt/PKB-Mediated Phosphorylation of Twist1 Promotes Tumor Metastasis via Mediating Cross-Talk between PI3K/Akt and TGF-β Signaling Axes
Cancer Discovery - Tập 2 Số 3 - Trang 248-259 - 2012
Gui-Rong Xue, David F. Restuccia, Qiang Lan, Debby Hynx, Stephan Dirnhofer, Daniel Heß, Curzio Rüegg, Brian A. Hemmings
Abstract Metastatic breast tumor cells display an epithelial–mesenchymal transition (EMT) that increases cell motility, invasion, and dissemination. Although the transcription factor Twist1 has been shown to contribute to EMT and cancer metastasis, the signaling pathways regulating Twist1 activity are poorly understood. Here, we show that Twist1 is u...... hiện toàn bộ
STK11/LKB1 Mutations and PD-1 Inhibitor Resistance in KRAS-Mutant Lung Adenocarcinoma
Cancer Discovery - Tập 8 Số 7 - Trang 822-835 - 2018
Ferdinandos Skoulidis, Michael E. Goldberg, Danielle Greenawalt, Matthew D. Hellmann, Mark M. Awad, Justin F. Gainor, Alexa B. Schrock, Ryan J. Hartmaier, Sally E. Trabucco, Laurie M. Gay, Siraj M. Ali, Julia A. Elvin, Gaurav Singal, Jeffrey S. Ross, David Fabrizio, Péter M. Szabó, Chang Han, Ariella Sasson, Sujaya Srinivasan, Stefan Kirov, Joseph D. Szustakowski, Patrik Vitazka, Robin Edwards, José A. Bufill, Neelesh Sharma, Sai‐Hong Ignatius Ou, Nir Peled, David R. Spigel, Hira Rizvi, Elizabeth Jiménez Aguilar, Brett W. Carter, Jeremy J. Erasmus, Darragh Halpenny, Andrew J. Plodkowski, Niamh M. Long, Mizuki Nishino, Warren L. Denning, Ana Galán‐Cobo, Haïfa Hamdi, Taghreed Hirz, Pan Tong, Jing Wang, Jaime Rodriguez‐Canales, Pamela Villalobos, Edwin R. Parra, Neda Kalhor, Lynette M. Sholl, Jennifer L. Sauter, Achim A. Jungbluth, Mari Mino‐Kenudson, Roxana Azimi, Yasir Y. Elamin, Jianjun Zhang, Giulia C. Leonardi, Fei Jiang, Kwok‐Kin Wong, John Lee, Vassiliki A. Papadimitrakopoulou, Ignacio I. Wistuba, Vincent A. Miller, Garrett M. Frampton, Jedd D. Wolchok, Alice T. Shaw, Pasi A. Jänne, Philip J. Stephens, Charles M. Rudin, William J. Geese, Lee A. Albacker, John V. Heymach
Abstract KRAS is the most common oncogenic driver in lung adenocarcinoma (LUAC). We previously reported that STK11/LKB1 (KL) or TP53 (KP) comutations define distinct subgroups of KRAS-mutant LUAC. Here, we examine the efficacy of PD-1 inhibitors in these subgroups. Objective response rates to PD-1 blockade differed significantly among KL (7.4%), KP (...... hiện toàn bộ
Real-Time Imaging Reveals Local, Transient Vascular Permeability, and Tumor Cell Intravasation Stimulated by TIE2hi Macrophage–Derived VEGFA
Cancer Discovery - Tập 5 Số 9 - Trang 932-943 - 2015
Allison S. Harney, Esther N. Arwert, David Entenberg, Yarong Wang, Peng Guo, Bin-Zhi Qian, Maja H. Oktay, Jeffrey W. Pollard, Joan G. Jones, John S. Condeelis
Abstract Dissemination of tumor cells is an essential step in metastasis. Direct contact between a macrophage, mammalian-enabled (MENA)–overexpressing tumor cell, and endothelial cell [Tumor MicroEnvironment of Metastasis (TMEM)] correlates with metastasis in breast cancer patients. Here we show, using intravital high-resolution two-photon microscopy...... hiện toàn bộ
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
nab-Paclitaxel Potentiates Gemcitabine Activity by Reducing Cytidine Deaminase Levels in a Mouse Model of Pancreatic Cancer
Cancer Discovery - Tập 2 Số 3 - Trang 260-269 - 2012
Natalie Cook, Albrecht Neeße, Tashinga E. Bapiro, Martijn P. Lolkema, Duncan I. Jodrell, David A. Tuveson
Abstract Nanoparticle albumin-bound (nab)-paclitaxel, an albumin-stabilized paclitaxel formulation, demonstrates clinical activity when administered in combination with gemcitabine in patients with metastatic pancreatic ductal adenocarcinoma (PDA). The limited availability of patient tissue and exquisite sensitivity of xenografts to chemotherapeutics...... 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
Response to MET Inhibitors in Patients with Stage IV Lung Adenocarcinomas Harboring MET Mutations Causing Exon 14 Skipping
Cancer Discovery - Tập 5 Số 8 - Trang 842-849 - 2015
Paul K. Paik, Alexander Drilon, Pang‐Dian Fan, Helena A. Yu, Natasha Rekhtman, Michelle S. Ginsberg, Laetitia Borsu, Nikolaus Schultz, Michael F. Berger, Charles M. Rudin, Marc Ladanyi
Abstract Mutations in the MET exon 14 RNA splice acceptor and donor sites, which lead to exon skipping, deletion of the juxtamembrane domain containing the CBL E3-ubiquitin ligase-binding site, and decreased turnover of the resultant aberrant MET protein, were previously reported to be oncogenic in preclinical models. We now report responses to the M...... hiện toàn bộ
Hallmarks of Cancer: New Dimensions
Cancer Discovery - Tập 12 Số 1 - Trang 31-46 - 2022
Douglas Hanahan
Abstract The hallmarks of cancer conceptualization is a heuristic tool for distilling the vast complexity of cancer phenotypes and genotypes into a provisional set of underlying principles. As knowledge of cancer mechanisms has progressed, other facets of the disease have emerged as potent...... hiện toàn bộ
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