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Cancer Discovery

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https://www.readbyqxmd.com/read/30322868/charities-fund-uk-eu-research-partnerships
#1
(no author information available yet)
Charities in the UK, Italy, and Spain awarded $39.4 million to six international cancer research projects, providing a post-Brexit model for collaboration. The 5-year awards will fund a variety of projects, such as investigations of targeted treatments for colorectal cancer.
October 15, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/30322867/integrative-molecular-characterization-of-malignant-pleural-mesothelioma
#2
Julija Hmeljak, Francisco Sanchez-Vega, Katherine A Hoadley, Juliann Shih, Chip Stewart, David I Heiman, Patrick Tarpey, Ludmila Danilova, Esther Drill, Ewan A Gibb, Reanne Bowlby, Rupa Kanchi, Hatice U Osmanbeyoglu, Yoshitaka Sekido, Jumpei Takeshita, Yulia Newton, Kiley Graim, Manaswi Gupta, Carl M Gay, Lixia Diao, David L Gibbs, Vesteinn Thorsson, Lisa Iype, Havish S Kantheti, David T Severson, Gloria Ravegnini, Patrice Desmeules, Achim A Jungbluth, William D Travis, Sanja Dacic, Lucian R Chirieac, Françoise Galateau-Salle, Junya Fujimoto, Aliya N Husain, Henrique C Silveira, Valerie W Rusch, Robert C Rintoul, Harvey Pass, Hedy Kindler, Marjorie G Zauderer, David J Kwiatkowski, Raphael Bueno, Anne S Tsao, Jenette Creaney, Tara Lichtenberg, Kristen Leraas, Jay Bowen, Tcga Research Network, Ina Felau, Jean Claude Zenklusen, Rehan Akbani, Andrew D Cherniack, Lauren Averett Byers, Michael S Noble, Jonathan A Fletcher, Gordon Robertson, Ronglai Shen, Hiroyuki Aburatani, Bruce Ws Robinson, Peter Campbell, Marc Ladanyi
Malignant pleural mesothelioma (MPM) is a highly lethal cancer of the lining of the chest cavity. To expand our understanding of MPM, we conducted a comprehensive integrated genomic study, including the most detailed analysis of BAP1 alterations to date. We identified histology-independent molecular prognostic subsets, and defined a novel genomic subtype with TP53 and SETDB1 mutations and extensive loss of heterozygosity. We also report strong expression of the immune checkpoint gene VISTA in epithelioid MPM, strikingly higher than in other solid cancers, with implications for the immune response to MPM and for its immunotherapy...
October 15, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/30314989/oncogenic-epithelial-reprogramming-drives-neuroendocrine-cancers
#3
(no author information available yet)
A set of oncogenic drivers induce the neuroendocrine reprogramming of prostate and lung epithelial cells.
October 12, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/30314988/technique-pinpoints-oncogenic-brca1-mutations
#4
(no author information available yet)
Researchers induced nearly 4,000 germline mutations in BRCA1 in human cells and tracked the effects. The results reveal that 21% of single-nucleotide variants they tested are likely oncogenic.
October 12, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/30314987/telisotuzumab-vedotin-has-activity-in-patients-with-met-positive-nsclc
#5
(no author information available yet)
The MET-targeting antibody-drug conjugate telisotuzumab vedotin (Teliso-V) is well tolerated in patients.
October 12, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/30314986/nih-budget-makes-up-ground
#6
(no author information available yet)
Since 2015, 4 consecutive years of substantial increases have expanded the NIH budget by a total of $9 billion, or 30%-a boost that has helped the agency close the gap on medical inflation. Most recently, Congress approved a $2 billion increase for fiscal year 2019, bringing the agency's total budget to $39.1 million.
October 12, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/30314985/c-kit-has-a-tumor-suppressive-role-via-induction-of-apoptosis
#7
(no author information available yet)
In addition to its oncogenic kinase activity, c-KIT acts as a dependence receptor to promote apoptosis.
October 12, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/30314984/mevalonate-pathway-inhibitors-may-be-effective-cancer-vaccine-adjuvants
#8
(no author information available yet)
Lipophilic statins and bisphosphonates may serve as potent adjuvants for cancer vaccines.
October 12, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/30314983/antibody-dependent-cellular-cytotoxicity-renders-macrophages-immunosuppressive
#9
(no author information available yet)
Therapeutic antibodies result in ADCP that upregulates PD-L1 and IDO on macrophages.
October 12, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/30309862/mouse-models-for-cancer-immunotherapy-research
#10
REVIEW
Brian Olson, Yadi Li, Yu Lin, Edison T Liu, Akash Patnaik
Immunotherapy has revolutionized cancer therapy, largely attributed to the success of immune-checkpoint blockade. However, there are subsets of patients across multiple cancers who have not shown robust responses to these agents. A major impediment to progress in the field is the availability of faithful mouse models that recapitulate the complexity of human malignancy and immune contexture within the tumor microenvironment. These models are urgently needed across all malignancies to interrogate and predict antitumor immune responses and therapeutic efficacy in clinical trials...
October 11, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/30305285/eif1ax-and-ras-mutations-cooperate-to-drive-thyroid-tumorigenesis-through-atf4-and-c-myc
#11
Gnana P Krishnamoorthy, Natalie R Davidson, Steven D Leach, Zhen Zhao, Scott W Lowe, Gina Lee, Iñigo Landa, James Nagarajah, Mahesh Saqcena, Kamini Singh, Hans-Guido Wendel, Snjezana Dogan, Prasanna P Tamarapu, John Blenis, Ronald Ghossein, Jeffrey A Knauf, Gunnar Rätsch, James A Fagin
Translation initiation is orchestrated by the cap binding and 43S pre-initiation complexes (PIC). Eukaryotic initiation factor 1A (EIF1A) is essential for recruitment of the ternary complex and for assembling the 43S PIC. Recurrent EIF1AX mutations in papillary thyroid cancers are mutually exclusive with other drivers, including RAS. EIF1AX is enriched in advanced thyroid cancers, where it displays a striking co-occurrence with RAS, which cooperates to induce tumorigenesis in mice and isogenic cell lines. The C-terminal EIF1AX-A113splice mutation is the most prevalent in advanced thyroid cancer...
October 10, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/30305284/study-atezolizumab-improves-survival-in-sclc
#12
(no author information available yet)
Combining the PD-L1 inhibitor atezolizumab with platinum-based chemotherapy improves overall survival among patients with extensive-stage small cell lung cancer relative to chemotherapy alone. These findings could lead to a new first-line treatment option for patients with the disease.
October 10, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/30297358/suppression-of-sting-associated-with-lkb1-loss-in-kras-driven-lung-cancer
#13
Shunsuke Kitajima, Elena Ivanova, Sujuan Guo, Ryohei Yoshida, Marco Campisi, Shriram K Sundararaman, Shoichiro Tange, Yoichiro Mitsuishi, Tran C Thai, Sayuri Masuda, Brandon P Piel, Lynette M Sholl, Paul T Kirschmeier, Cloud P Paweletz, Hideo Watanabe, Mamiko Yajima, David A Barbie
KRAS-driven lung cancers frequently inactivate TP53 and/or STK11/LKB1, defining tumor subclasses with emerging clinical relevance. Specifically, KRAS-LKB1 (KL) mutant lung cancers are particularly aggressive, lack PD-L1, and respond poorly to immune checkpoint blockade (ICB). The mechanistic basis for this impaired immunogenicity, despite the overall high mutational load of KRAS mutant lung cancers, remains obscure. Here we report that LKB1 loss results in marked silencing of STING expression and insensitivity to cytoplasmic double strand DNA (dsDNA) sensing...
October 8, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/30291129/lurbinectedin-is-active-in-patients-with-brca1-2-mutant-breast-cancer
#14
(no author information available yet)
A phase II trial evaluated lurbinectedin in patients with BRCA1/2 -mutant and wild-type tumors.
October 5, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/30291128/defective-nuclear-envelope-assembly-may-promote-mitotic-errors
#15
(no author information available yet)
Defective assembly of the nuclear envelope and nuclear pore complex in micronuclei may underlie chromothripsis.
October 5, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/30291127/better-standards-sought-for-predictive-immunotherapy-biomarkers
#16
(no author information available yet)
Predictive biomarkers of immunotherapy are growing increasingly complex-incorporating aspects of tumor-intrinsic, immune microenvironmental, and host-related biology-and several new initiatives aim to establish standards for the field to ensure consistency of commercial assays going forward.
October 5, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/30291126/epacadostat-plus-pembrolizumab-is-well-tolerated-in-a-phase-i-trial
#17
(no author information available yet)
Epacadostat plus pembrolizumab achieved responses in 40% of patients with advanced solid tumors.
October 5, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/30291125/neutrophil-extracellular-traps-trigger-dormant-tumor-cell-proliferation
#18
(no author information available yet)
Inflammation-induced neutrophil extracellular traps (NET) awaken dormant cells to promote metastasis.
October 5, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/30291124/car-t-cell-therapy-for-solid-tumors
#19
(no author information available yet)
Scientists have identified a wide variety of challenges preventing the development of effective CAR T-cell therapies for solid tumors, but they are investigating just as many potential solutions. Progress has been slow, but many researchers remain optimistic that successful CAR T-cell therapies, either alone or in combination with other treatments, will eventually be developed.
October 5, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/30279173/remodeling-of-the-collagen-matrix-in-aging-skin-promotes-melanoma-metastasis-and-affects-immune-cell-motility
#20
Amanpreet Kaur, Brett L Ecker, Stephen M Douglass, Curtis H Kugel, Marie R Webster, Filipe V Almeida, Rajasekharan Somasundaram, James Hayden, Ehsan Ban, Hossein Ahmadzadeh, Janusz Franco-Barraza, Neelima Shah, Ian A Mellis, Frederick Keeney, Andrew Kossenkov, Hsin-Yao Tang, Xiangfan Yin, Qin Liu, Xiaowei Xu, Mitchell Fane, Patricia Brafford, Meenhard Herlyn, David W Speicher, Jennifer A Wargo, Michael T Tetzlaff, Lauren E Haydu, Arjun Raj, Vivek Shenoy, Edna Cukierman, Ashani T Weeraratna
Physical changes in skin are among the most visible signs of aging. We found that young dermal fibroblasts secrete high levels of extracellular matrix (ECM) constituents, including proteoglycans, glycoproteins and cartilage-linking proteins. The most abundantly secreted was HAPLN1, a hyaluronic and proteoglycan link protein. HAPLN1 was lost in aged fibroblasts, resulting in a more aligned ECM that promoted metastasis of melanoma cells. Reconstituting HAPLN1 inhibited metastasis in an aged microenvironment, in 3D skin reconstruction models, and in vivo...
October 2, 2018: Cancer Discovery
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