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Cancer Discovery

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https://www.readbyqxmd.com/read/28228393/protein-turnover-provides-pancreatic-cancer-target
#1
(no author information available yet)
Decreased activity of the chromatin remodeling factor gene SMARCB1 drives a switch in pancreatic cancer cells toward a more aggressive, mesenchymal state. This change makes the tumors more susceptible to drugs that target protein metabolism and associated stress responses.
February 22, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28228392/idh-mutant-tumors-vulnerable-to-parp-inhibition
#2
(no author information available yet)
Several cancers, including glioma and acute myeloid leukemia, carry mutations in IDH1 or IDH2 Researchers have found that these mutations impair homologous recombination, making the tumors sensitive to PARP inhibition. They showed that one such inhibitor, olaparib, killed IDH1/2-mutant cancer cells in culture and slowed tumor growth in mice.
February 22, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28213356/otx2-activity-at-distal-regulatory-elements-shapes-the-chromatin-landscape-of-group-3-medulloblastoma
#3
Gaylor Boulay, Mary E Awad, Nicolo Riggi, Tenley C Archer, Sowmya Iyer, Wannaporn E Boonseng, Nikki E Rossetti, Beverly Naigles, Shruthi Rengarajan, Angela Volorio, James C Kim, Jill P Mesirov, Pablo Tamayo, Scott L Pomeroy, Martin J Aryee, Miguel N Rivera
Medulloblastoma is the most frequent malignant pediatric brain tumor and is divided into at least four subgroups known as WNT, SHH, Group 3, and Group 4. Here, we characterized gene regulation mechanisms in the most aggressive subtype, Group 3 tumors, through genome-wide chromatin and expression profiling. Our results show that most active distal sites in these tumors are occupied by the transcription factor OTX2. Highly active OTX2-bound enhancers are often arranged as clusters of adjacent peaks and are also bound by the transcription factor NEUROD1...
February 17, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28213355/chd1-is-a-synthetic-essential-gene-in-pten-deficient-prostate-cancer
#4
(no author information available yet)
CHD1 is required for the growth of PTEN-deficient prostate cancer cells in vitro and in vivo.
February 17, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28213354/a-population-of-innate-lymphoid-cells-impairs-til-expansion-in-hgsc
#5
(no author information available yet)
Regulatory CD56(+)CD3(-) innate lymphoid cells (ILC) suppress tumor-infiltrating lymphocyte (TIL) expansion.
February 17, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28213353/the-telomere-associated-tzap-protein-limits-telomere-length
#6
(no author information available yet)
TZAP binds preferentially to long telomeres and promotes telomere trimming.
February 17, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28213352/extrachromosomal-dna-amplifications-increase-oncogene-copy-number
#7
(no author information available yet)
Circular extrachromosomal DNA (ecDNA) amplifications promote tumor heterogeneity and evolution.
February 17, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28213351/mycn-drives-rb-null-retinoblastoma-initiation
#8
(no author information available yet)
Overexpression of MYCN overcomes a proliferative block to drive RB-deficient retinoblastoma.
February 17, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28202625/gut-microbiota-promotes-obesity-associated-liver-cancer-through-pge2-mediated-suppression-of-antitumor-immunity
#9
Tze Mun Loo, Fumitaka Kamachi, Yoshihiro Watanabe, Shin Yoshimoto, Hiroaki Kanda, Yuriko Arai, Yaeko Nakajima-Takagi, Atsushi Iwama, Tomoaki Koga, Yukihiko Sugimoto, Takayuki Ozawa, Masaru Nakamura, Miho Kumagai, Koichi Watashi, Makoto M Taketo, Tomohiro Aoki, Shuh Narumiya, Masanobu Oshima, Makoto Arita, Eiji Hara, Naoko Ohtani
Obesity increases the risk of cancers, including hepatocellular carcinomas (HCCs). However, the precise molecular mechanisms through which obesity promotes HCC development are still unclear. Recent studies have shown that gut microbiota may influence liver diseases by transferring its metabolites and components. Here, we show that the hepatic translocation of obesity-induced lipoteichoic acid (LTA), a Gram positive gut microbial component, promotes HCC development by creating a tumor-promoting microenvironment...
February 15, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28193780/an-essential-gene-dataset-defines-functional-gene-networks
#10
(no author information available yet)
Gene essentiality pattern analysis can identify gene interactions and synthetic lethal interactions.
February 13, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28193779/combination-targeted-therapy-to-disrupt-aberrant-oncogenic-signaling-and-reverse-epigenetic-dysfunction-in-idh2-and-tet2-mutant-acute-myeloid-leukemia
#11
Alan H Shih, Cem Meydan, Kaitlyn Shank, Francine E Garrett-Bakelman, Patrick S Ward, Andrew Intlekofer, Abbas Nazir, Eytan Stein, Kristina Knapp, Jacob Glass, Jeremy Travins, Kim Straley, Camelia Gliser, Chris Mason, Katharine Yen, Craig B Thompson, Ari Melnick, Ross L Levine
Genomic studies in acute myeloid leukemias (AML) have identified mutations which drive altered DNA methylation, including TET2 and IDH2. Here we show that models of AMLs resulting from TET2 or IDH2 mutations combined with FLT3ITD mutations are sensitive to 5-Azacytidine or to the IDH2 inhibitor AG-221, respectively. 5-Azacytidine and AG-221 treatment induced an attenuation of aberrant DNA methylation and transcriptional output, and resulted in a reduction in leukemic blasts consistent with anti-leukemic activity...
February 13, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28193778/ag-221-a-first-in-class-therapy-targeting-acute-myeloid-leukemia-harboring-oncogenic-idh2-mutations
#12
Katharine Yen, Jeremy Travins, Fang Wang, Muriel D David, Erin Artin, Kim Straley, Anil Padyana, Stefan Gross, Byron DeLaBarre, Erica Tobin, Yue Chen, Raj Nagaraja, Sung Choe, Lei Jin, Zenon Konteatis, Giovanni Cianchetta, Jeffrey O Saunders, Francesco G Salituro, Cyril Quivoron, Paule Opolon, Olivia Bawa, Véronique Saada, Angelo Paci, Sophie Broutin, Olivier A Bernard, Stéphane de Botton, Benoît S Marteyn, Monika Pilichowska, YingXia Xu, Cheng Fang, Fan Jiang, Wentao Wei, Shengfang Jin, Lee Silverman, Wei Liu, Hua Yang, Lenny Dang, Marion Dorsch, Virginie Penard-Lacronique, Scott A Biller, Shin-San Michael Su
Somatic gain-of-function mutations in isocitrate dehydrogenase (IDH) 1 and 2 are found in multiple hematologic and solid tumors, leading to accumulation of the oncometabolite, (R)-2-hydroxyglutarate (2HG). 2HG competitively inhibits α-ketoglutarate-dependent dioxygenases, including histone demethylases and methylcytosine dioxygenases of the Tet family, causing epigenetic dysregulation and a block in cellular differentiation. In vitro studies have provided proof of concept for mutant IDH inhibition as a therapeutic approach...
February 13, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28193777/tracing-the-path-of-car-t-cells
#13
(no author information available yet)
Adding a radioactive tag to CAR T cells has allowed these engineered cells to be monitored as they home in on brain tumors in patients. The technique could help promote a deeper understanding of why this immunotherapy isn't more broadly effective, and why resistance sometimes develops.
February 13, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28193776/ube2o-inhibition-restores-ampk%C3%AE-2-levels-to-impair-tumorigenesis
#14
(no author information available yet)
Ube2o deletion suppresses the growth of breast and prostate cancers and extends survival in mice.
February 13, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28193775/targeting-the-eed-h3k27me3-interaction-allosterically-inhibits-prc2
#15
(no author information available yet)
EED226 and A-395 bind to the H3K27me3 binding pocket of EED to allosterically inhibit PRC2.
February 13, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28193774/universal-car-t-cells-successfully-treat-leukemia
#16
(no author information available yet)
Two infants with relapsed, refractory B-cell acute lymphoblastic leukemia went into complete remission after being treated with CD19-targeting CAR T cells derived from an unmatched donor. The study is the first to demonstrate that a universal form of CAR T-cell therapy can be safely utilized.
February 13, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28193773/dna-methylation-analysis-shows-epigenetic-heterogeneity-in-ewing-sarcoma
#17
(no author information available yet)
Ewing sarcoma is epigenetically heterogeneous despite the lack of genomic heterogeneity.
February 13, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28193772/the-dna-pkcs-structure-suggests-dsb-repair-is-allosterically-regulated
#18
(no author information available yet)
The structure of DNA-PKcs in complex with KU80 suggests KU80 promotes allosteric activation of DNA-PKcs.
February 13, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28193771/ceritinib-bests-chemo-for-untreated-alk-nsclc
#19
(no author information available yet)
Patients with ALK-positive non-small cell lung cancer may soon have a new first-line treatment option in ceritinib, which outperformed chemotherapy in a phase III study. However, toxicity issues remain a problem for ceritinib, and another next-generation ALK inhibitor, alectinib, is more likely to become the drug of choice for untreated patients.
February 13, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28188128/interaction-landscape-of-inherited-polymorphisms-with-somatic-events-in-cancer
#20
Hannah Carter, Rachel Marty, Matan Hofree, Andy Gross, James Jensen, Kathleen M Fisch, Xingyu Wu, Christopher DeBoever, Eric L Van Nostrand, Yan Song, Emily Wheeler, Jason F Kreisberg, Scott M Lippman, Gene Yeo, J Silvio Gutkind, Trey Ideker
Recent studies have characterized the extensive somatic alterations that arise during cancer. However, the somatic evolution of a tumor may be significantly affected by inherited polymorphisms carried in the germline. Here, we analyze genomic data for 5954 tumors to reveal and systematically validate 412 genetic interactions between germline polymorphisms and major somatic events, including tumor formation in specific tissues and alteration of specific cancer genes. Among germline-somatic interactions, we find germline variants in RBFOX1 that increase incidence of SF3B1 somatic mutation by eight-fold via functional alterations in RNA splicing...
February 10, 2017: Cancer Discovery
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